Targeting the Renin-Angiotensin System (RAS) for Neuropsychiatric Disorders

  • Autores: de Miranda A.1, Macedo D.2, Rocha N.3, Teixeira A.4
  • Afiliações:
    1. Faculty of Medicine, Interdisciplinary Laboratory of Medical Investigation (LIIM)
    2. Department of Physiology and Pharmacology, Neuropharmacology Laboratory, Drug Research, and Development Center, Faculty of Medicine, Federal University of Ceara
    3. Department of Neurology, The Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, McGovern Medical School, University of Texas Health Science Center at Houston
    4. Department of Psychiatry and Behavioral Sciences, Neuropsychiatry Program, McGovern Medical School, University of Texas Health Science Center at Houston
  • Edição: Volume 22, Nº 1 (2024)
  • Páginas: 107-122
  • Seção: Neurology
  • URL: https://rjpbr.com/1570-159X/article/view/644241
  • DOI: https://doi.org/10.2174/1570159X20666220927093815
  • ID: 644241

Citar

Texto integral

Resumo

Background:Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer’s disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic targets.

Objective:We aim to report current experimental and clinical evidence on the role of RAS in physiology and pathophysiology of mood disorders, schizophrenia, AD and related dementias. We also aim to discuss bottlenecks and future perspectives that can foster the development of new related therapeutic strategies.

Conclusion:The available evidence supports positive therapeutic effects for neuropsychiatric disorders with the inhibition/antagonism of the ACE/Ang II/AT1 receptor axis or the activation of the ACE2/Ang-(1-7)/Mas receptor axis. Most of this evidence comes from pre-clinical studies and clinical studies lag much behind, hampering a potential translation into clinical practice.

Sobre autores

Aline de Miranda

Faculty of Medicine, Interdisciplinary Laboratory of Medical Investigation (LIIM)

Autor responsável pela correspondência
Email: info@benthamscience.net

Danielle Macedo

Department of Physiology and Pharmacology, Neuropharmacology Laboratory, Drug Research, and Development Center, Faculty of Medicine, Federal University of Ceara

Email: info@benthamscience.net

Natalia Rocha

Department of Neurology, The Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, McGovern Medical School, University of Texas Health Science Center at Houston

Email: info@benthamscience.net

Antonio Teixeira

Department of Psychiatry and Behavioral Sciences, Neuropsychiatry Program, McGovern Medical School, University of Texas Health Science Center at Houston

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Kahn, R.S.; Sommer, I.E.; Murray, R.M.; Meyer-Lindenberg, A.; Weinberger, D.R.; Cannon, T.D.; O’Donovan, M.; Correll, C.U.; Kane, J.M.; van Os, J.; Insel, T.R. Schizophrenia. Nat. Rev. Dis. Primers, 2015, 1(1), 15067. doi: 10.1038/nrdp.2015.67 PMID: 27189524
  2. James, S.L.; Abate, D.; Abate, K.H.; Abay, S.M.; Abbafati, C.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdela, J.; Abdelalim, A.; Abdollahpour, I.; Abdulkader, R.S.; Abebe, Z.; Abera, S.F.; Abil, O.Z.; Abraha, H.N.; Abu-Raddad, L.J.; Abu-Rmeileh, N.M.E.; Accrombessi, M.M.K.; Acharya, D.; Acharya, P.; Ackerman, I.N.; Adamu, A.A.; Adebayo, O.M.; Adekanmbi, V.; Adetokunboh, O.O.; Adib, M.G.; Adsuar, J.C.; Afanvi, K.A.; Afarideh, M.; Afshin, A.; Agarwal, G.; Agesa, K.M.; Aggarwal, R.; Aghayan, S.A.; Agrawal, S.; Ahmadi, A.; Ahmadi, M.; Ahmadieh, H.; Ahmed, M.B.; Aichour, A.N.; Aichour, I.; Aichour, M.T.E.; Akinyemiju, T.; Akseer, N.; Al-Aly, Z.; Al-Eyadhy, A.; Al-Mekhlafi, H.M.; Al-Raddadi, R.M.; Alahdab, F.; Alam, K.; Alam, T.; Alashi, A.; Alavian, S.M.; Alene, K.A.; Alijanzadeh, M.; Alizadeh-Navaei, R.; Aljunid, S.M.; Alkerwi, A.; Alla, F.; Allebeck, P.; Alouani, M.M.L.; Altirkawi, K.; Alvis-Guzman, N.; Amare, A.T.; Aminde, L.N.; Ammar, W.; Amoako, Y.A.; Anber, N.H.; Andrei, C.L.; Androudi, S.; Animut, M.D.; Anjomshoa, M.; Ansha, M.G.; Antonio, C.A.T.; Anwari, P.; Arabloo, J.; Arauz, A.; Aremu, O.; Ariani, F.; Armoon, B.; Ärnlöv, J.; Arora, A.; Artaman, A.; Aryal, K.K.; Asayesh, H.; Asghar, R.J.; Ataro, Z.; Atre, S.R.; Ausloos, M.; Avila-Burgos, L.; Avokpaho, E.F.G.A.; Awasthi, A.; Ayala Quintanilla, B.P.; Ayer, R.; Azzopardi, P.S.; Babazadeh, A.; Badali, H.; Badawi, A.; Bali, A.G.; Ballesteros, K.E.; Ballew, S.H.; Banach, M.; Banoub, J.A.M.; Banstola, A.; Barac, A.; Barboza, M.A.; Barker-Collo, S.L.; Bärnighausen, T.W.; Barrero, L.H.; Baune, B.T.; Bazargan-Hejazi, S.; Bedi, N.; Beghi, E.; Behzadifar, M.; Behzadifar, M.; Béjot, Y.; Belachew, A.B.; Belay, Y.A.; Bell, M.L.; Bello, A.K.; Bensenor, I.M.; Bernabe, E.; Bernstein, R.S.; Beuran, M.; Beyranvand, T.; Bhala, N.; Bhattarai, S.; Bhaumik, S.; Bhutta, Z.A.; Biadgo, B.; Bijani, A.; Bikbov, B.; Bilano, V.; Bililign, N.; Bin Sayeed, M.S.; Bisanzio, D.; Blacker, B.F.; Blyth, F.M.; Bou-Orm, I.R.; Boufous, S.; Bourne, R.; Brady, O.J.; Brainin, M.; Brant, L.C.; Brazinova, A.; Breitborde, N.J.K.; Brenner, H.; Briant, P.S.; Briggs, A.M.; Briko, A.N.; Britton, G.; Brugha, T.; Buchbinder, R.; Busse, R.; Butt, Z.A.; Cahuana-Hurtado, L.; Cano, J.; Cárdenas, R.; Carrero, J.J.; Carter, A.; Carvalho, F.; Castañeda-Orjuela, C.A.; Castillo, R.J.; Castro, F.; Catalá-López, F.; Cercy, K.M.; Cerin, E.; Chaiah, Y.; Chang, A.R.; Chang, H-Y.; Chang, J-C.; Charlson, F.J.; Chattopadhyay, A.; Chattu, V.K.; Chaturvedi, P.; Chiang, P.P-C.; Chin, K.L.; Chitheer, A.; Choi, J-Y.J.; Chowdhury, R.; Christensen, H.; Christopher, D.J.; Cicuttini, F.M.; Ciobanu, L.G.; Cirillo, M.; Claro, R.M.; Collado-Mateo, D.; Cooper, C.; Coresh, J.; Cortesi, P.A.; Cortinovis, M.; Costa, M.; Cousin, E.; Criqui, M.H.; Cromwell, E.A.; Cross, M.; Crump, J.A.; Dadi, A.F.; Dandona, L.; Dandona, R.; Dargan, P.I.; Daryani, A.; Das Gupta, R.; Das Neves, J.; Dasa, T.T.; Davey, G.; Davis, A.C.; Davitoiu, D.V.; De Courten, B.; De La Hoz, F.P.; De Leo, D.; De Neve, J-W.; Degefa, M.G.; Degenhardt, L.; Deiparine, S.; Dellavalle, R.P.; Demoz, G.T.; Deribe, K.; Dervenis, N.; Des Jarlais, D.C.; Dessie, G.A.; Dey, S.; Dharmaratne, S.D.; Dinberu, M.T.; Dirac, M.A.; Djalalinia, S.; Doan, L.; Dokova, K.; Doku, D.T.; Dorsey, E.R.; Doyle, K.E.; Driscoll, T.R.; Dubey, M.; Dubljanin, E.; Duken, E.E.; Duncan, B.B.; Duraes, A.R.; Ebrahimi, H.; Ebrahimpour, S.; Echko, M.M.; Edvardsson, D.; Effiong, A.; Ehrlich, J.R.; El Bcheraoui, C.; El Sayed Zaki, M.; El-Khatib, Z.; Elkout, H.; Elyazar, I.R.F.; Enayati, A.; Endries, A.Y.; Er, B.; Erskine, H.E.; Eshrati, B.; Eskandarieh, S.; Esteghamati, A.; Esteghamati, S.; Fakhim, H.; Fallah Omrani, V.; Faramarzi, M.; Fareed, M.; Farhadi, F.; Farid, T.A.; Farinha, C.S.E.; Farioli, A.; Faro, A.; Farvid, M.S.; Farzadfar, F.; Feigin, V.L.; Fentahun, N.; Fereshtehnejad, S-M.; Fernandes, E.; Fernandes, J.C.; Ferrari, A.J.; Feyissa, G.T.; Filip, I.; Fischer, F.; Fitzmaurice, C.; Foigt, N.A.; Foreman, K.J.; Fox, J.; Frank, T.D.; Fukumoto, T.; Fullman, N.; Fürst, T.; Furtado, J.M.; Futran, N.D.; Gall, S.; Ganji, M.; Gankpe, F.G.; Garcia-Basteiro, A.L.; Gardner, W.M.; Gebre, A.K.; Gebremedhin, A.T.; Gebremichael, T.G.; Gelano, T.F.; Geleijnse, J.M.; Genova-Maleras, R.; Geramo, Y.C.D.; Gething, P.W.; Gezae, K.E.; Ghadiri, K.; Ghasemi, F.K.; Ghasemi-Kasman, M.; Ghimire, M.; Ghosh, R.; Ghoshal, A.G.; Giampaoli, S.; Gill, P.S.; Gill, T.K.; Ginawi, I.A.; Giussani, G.; Gnedovskaya, E.V.; Goldberg, E.M.; Goli, S.; Gómez-Dantés, H.; Gona, P.N.; Gopalani, S.V.; Gorman, T.M.; Goulart, A.C.; Goulart, B.N.G.; Grada, A.; Grams, M.E.; Grosso, G.; Gugnani, H.C.; Guo, Y.; Gupta, P.C.; Gupta, R.; Gupta, R.; Gupta, T.; Gyawali, B.; Haagsma, J.A.; Hachinski, V.; Hafezi-Nejad, N.; Haghparast Bidgoli, H.; Hagos, T.B.; Hailu, G.B.; Haj-Mirzaian, A.; Haj-Mirzaian, A.; Hamadeh, R.R.; Hamidi, S.; Handal, A.J.; Hankey, G.J.; Hao, Y.; Harb, H.L.; Harikrishnan, S.; Haro, J.M.; Hasan, M.; Hassankhani, H.; Hassen, H.Y.; Havmoeller, R.; Hawley, C.N.; Hay, R.J.; Hay, S.I.; Hedayatizadeh-Omran, A.; Heibati, B.; Hendrie, D.; Henok, A.; Herteliu, C.; Heydarpour, S.; Hibstu, D.T.; Hoang, H.T.; Hoek, H.W.; Hoffman, H.J.; Hole, M.K.; Homaie Rad, E.; Hoogar, P.; Hosgood, H.D.; Hosseini, S.M.; Hosseinzadeh, M.; Hostiuc, M.; Hostiuc, S.; Hotez, P.J.; Hoy, D.G.; Hsairi, M.; Htet, A.S.; Hu, G.; Huang, J.J.; Huynh, C.K.; Iburg, K.M.; Ikeda, C.T.; Ileanu, B.; Ilesanmi, O.S.; Iqbal, U.; Irvani, S.S.N.; Irvine, C.M.S.; Islam, S.M.S.; Islami, F.; Jacobsen, K.H.; Jahangiry, L.; Jahanmehr, N.; Jain, S.K.; Jakovljevic, M.; Javanbakht, M.; Jayatilleke, A.U.; Jeemon, P.; Jha, R.P.; Jha, V.; Ji, J.S.; Johnson, C.O.; Jonas, J.B.; Jozwiak, J.J.; Jungari, S.B.; Jürisson, M.; Kabir, Z.; Kadel, R.; Kahsay, A.; Kalani, R.; Kanchan, T.; Karami, M.; Karami Matin, B.; Karch, A.; Karema, C.; Karimi, N.; Karimi, S.M.; Kasaeian, A.; Kassa, D.H.; Kassa, G.M.; Kassa, T.D.; Kassebaum, N.J.; Katikireddi, S.V.; Kawakami, N.; Karyani, A.K.; Keighobadi, M.M.; Keiyoro, P.N.; Kemmer, L.; Kemp, G.R.; Kengne, A.P.; Keren, A.; Khader, Y.S.; Khafaei, B.; Khafaie, M.A.; Khajavi, A.; Khalil, I.A.; Khan, E.A.; Khan, M.S.; Khan, M.A.; Khang, Y-H.; Khazaei, M.; Khoja, A.T.; Khosravi, A.; Khosravi, M.H.; Kiadaliri, A.A.; Kiirithio, D.N.; Kim, C-I.; Kim, D.; Kim, P.; Kim, Y-E.; Kim, Y.J.; Kimokoti, R.W.; Kinfu, Y.; Kisa, A.; Kissimova-Skarbek, K.; Kivimäki, M.; Knudsen, A.K.S.; Kocarnik, J.M.; Kochhar, S.; Kokubo, Y.; Kolola, T.; Kopec, J.A.; Kosen, S.; Kotsakis, G.A.; Koul, P.A.; Koyanagi, A.; Kravchenko, M.A.; Krishan, K.; Krohn, K.J.; Kuate, Defo B.; Kucuk Bicer, B.; Kumar, G.A.; Kumar, M.; Kyu, H.H.; Lad, D.P.; Lad, S.D.; Lafranconi, A.; Lalloo, R.; Lallukka, T.; Lami, F.H.; Lansingh, V.C.; Latifi, A.; Lau, K.M-M.; Lazarus, J.V.; Leasher, J.L.; Ledesma, J.R.; Lee, P.H.; Leigh, J.; Leung, J.; Levi, M.; Lewycka, S.; Li, S.; Li, Y.; Liao, Y.; Liben, M.L.; Lim, L-L.; Lim, S.S.; Liu, S.; Lodha, R.; Looker, K.J.; Lopez, A.D.; Lorkowski, S.; Lotufo, P.A.; Low, N.; Lozano, R.; Lucas, T.C.D.; Lucchesi, L.R.; Lunevicius, R.; Lyons, R.A.; Ma, S.; Macarayan, E.R.K.; Mackay, M.T.; Madotto, F.; Magdy Abd El Razek, H.; Magdy Abd El Razek, M.; Maghavani, D.P.; Mahotra, N.B.; Mai, H.T.; Majdan, M.; Majdzadeh, R.; Majeed, A.; Malekzadeh, R.; Malta, D.C.; Mamun, A.A.; Manda, A-L.; Manguerra, H.; Manhertz, T.; Mansournia, M.A.; Mantovani, L.G.; Mapoma, C.C.; Maravilla, J.C.; Marcenes, W.; Marks, A.; Martins-Melo, F.R.; Martopullo, I.; März, W.; Marzan, M.B.; Mashamba-Thompson, T.P.; Massenburg, B.B.; Mathur, M.R.; Matsushita, K.; Maulik, P.K.; Mazidi, M.; McAlinden, C.; McGrath, J.J.; McKee, M.; Mehndiratta, M.M.; Mehrotra, R.; Mehta, K.M.; Mehta, V.; Mejia-Rodriguez, F.; Mekonen, T.; Melese, A.; Melku, M.; Meltzer, M.; Memiah, P.T.N.; Memish, Z.A.; Mendoza, W.; Mengistu, D.T.; Mengistu, G.; Mensah, G.A.; Mereta, S.T.; Meretoja, A.; Meretoja, T.J.; Mestrovic, T.; Mezerji, N.M.G.; Miazgowski, B.; Miazgowski, T.; Millear, A.I.; Miller, T.R.; Miltz, B.; Mini, G.K.; Mirarefin, M.; Mirrakhimov, E.M.; Misganaw, A.T.; Mitchell, P.B.; Mitiku, H.; Moazen, B.; Mohajer, B.; Mohammad, K.A.; Mohammadifard, N.; Mohammadnia-Afrouzi, M.; Mohammed, M.A.; Mohammed, S.; Mohebi, F.; Moitra, M.; Mokdad, A.H.; Molokhia, M.; Monasta, L.; Moodley, Y.; Moosazadeh, M.; Moradi, G.; Moradi-Lakeh, M.; Moradinazar, M.; Moraga, P.; Morawska, L.; Moreno Velásquez, I.; Morgado-Da-Costa, J.; Morrison, S.D.; Moschos, M.M.; Mountjoy-Venning, W.C.; Mousavi, S.M.; Mruts, K.B.; Muche, A.A.; Muchie, K.F.; Mueller, U.O.; Muhammed, O.S.; Mukhopadhyay, S.; Muller, K.; Mumford, J.E.; Murhekar, M.; Musa, J.; Musa, K.I.; Mustafa, G.; Nabhan, A.F.; Nagata, C.; Naghavi, M.; Naheed, A.; Nahvijou, A.; Naik, G.; Naik, N.; Najafi, F.; Naldi, L.; Nam, H.S.; Nangia, V.; Nansseu, J.R.; Nascimento, B.R.; Natarajan, G.; Neamati, N.; Negoi, I.; Negoi, R.I.; Neupane, S.; Newton, C.R.J.; Ngunjiri, J.W.; Nguyen, A.Q.; Nguyen, H.T.; Nguyen, H.L.T.; Nguyen, H.T.; Nguyen, L.H.; Nguyen, M.; Nguyen, N.B.; Nguyen, S.H.; Nichols, E.; Ningrum, D.N.A.; Nixon, M.R.; Nolutshungu, N.; Nomura, S.; Norheim, O.F.; Noroozi, M.; Norrving, B.; Noubiap, J.J.; Nouri, H.R.; Nourollahpour Shiadeh, M.; Nowroozi, M.R.; Nsoesie, E.O.; Nyasulu, P.S.; Odell, C.M.; Ofori-Asenso, R.; Ogbo, F.A.; Oh, I-H.; Oladimeji, O.; Olagunju, A.T.; Olagunju, T.O.; Olivares, P.R.; Olsen, H.E.; Olusanya, B.O.; Ong, K.L.; Ong, S.K.; Oren, E.; Ortiz, A.; Ota, E.; Otstavnov, S.S.; Øverland, S.; Owolabi, M.O.; P A, M.; Pacella, R.; Pakpour, A.H.; Pana, A.; Panda-Jonas, S.; Parisi, A.; Park, E-K.; Parry, C.D.H.; Patel, S.; Pati, S.; Patil, S.T.; Patle, A.; Patton, G.C.; Paturi, V.R.; Paulson, K.R.; Pearce, N.; Pereira, D.M.; Perico, N.; Pesudovs, K.; Pham, H.Q.; Phillips, M.R.; Pigott, D.M.; Pillay, J.D.; Piradov, M.A.; Pirsaheb, M.; Pishgar, F.; Plana-Ripoll, O.; Plass, D.; Polinder, S.; Popova, S.; Postma, M.J.; Pourshams, A.; Poustchi, H.; Prabhakaran, D.; Prakash, S.; Prakash, V.; Purcell, C.A.; Purwar, M.B.; Qorbani, M.; Quistberg, D.A.; Radfar, A.; Rafay, A.; Rafiei, A.; Rahim, F.; Rahimi, K.; Rahimi-Movaghar, A.; Rahimi-Movaghar, V.; Rahman, M.; Rahman, M.H.; Rahman, M.A.; Rahman, S.U.; Rai, R.K.; Rajati, F.; Ram, U.; Ranjan, P.; Ranta, A.; Rao, P.C.; Rawaf, D.L.; Rawaf, S.; Reddy, K.S.; Reiner, R.C.; Reinig, N.; Reitsma, M.B.; Remuzzi, G.; Renzaho, A.M.N.; Resnikoff, S.; Rezaei, S.; Rezai, M.S.; Ribeiro, A.L.P.; Roberts, N.L.S.; Robinson, S.R.; Roever, L.; Ronfani, L.; Roshandel, G.; Rostami, A.; Roth, G.A.; Roy, A.; Rubagotti, E.; Sachdev, P.S.; Sadat, N.; Saddik, B.; Sadeghi, E.; Saeedi, M.S.; Safari, H.; Safari, Y.; Safari-Faramani, R.; Safdarian, M.; Safi, S.; Safiri, S.; Sagar, R.; Sahebkar, A.; Sahraian, M.A.; Sajadi, H.S.; Salam, N.; Salama, J.S.; Salamati, P.; Saleem, K.; Saleem, Z.; Salimi, Y.; Salomon, J.A.; Salvi, S.S.; Salz, I.; Samy, A.M.; Sanabria, J.; Sang, Y.; Santomauro, D.F.; Santos, I.S.; Santos, J.V.; Santric, M.M.M.; Sao Jose, B.P.; Sardana, M.; Sarker, A.R.; Sarrafzadegan, N.; Sartorius, B.; Sarvi, S.; Sathian, B.; Satpathy, M.; Sawant, A.R.; Sawhney, M.; Saxena, S.; Saylan, M.; Schaeffner, E.; Schmidt, M.I.; Schneider, I.J.C.; Schöttker, B.; Schwebel, D.C.; Schwendicke, F.; Scott, J.G.; Sekerija, M.; Sepanlou, S.G.; Serván-Mori, E.; Seyedmousavi, S.; Shabaninejad, H.; Shafieesabet, A.; Shahbazi, M.; Shaheen, A.A.; Shaikh, M.A.; Shams-Beyranvand, M.; Shamsi, M.; Shamsizadeh, M.; Sharafi, H.; Sharafi, K.; Sharif, M.; Sharif-Alhoseini, M.; Sharma, M.; Sharma, R.; She, J.; Sheikh, A.; Shi, P.; Shibuya, K.; Shigematsu, M.; Shiri, R.; Shirkoohi, R.; Shishani, K.; Shiue, I.; Shokraneh, F.; Shoman, H.; Shrime, M.G.; Si, S.; Siabani, S.; Siddiqi, T.J.; Sigfusdottir, I.D.; Sigurvinsdottir, R.; Silva, J.P.; Silveira, D.G.A.; Singam, N.S.V.; Singh, J.A.; Singh, N.P.; Singh, V.; Sinha, D.N.; Skiadaresi, E.; Slepak, E.L.N.; Sliwa, K.; Smith, D.L.; Smith, M.; Soares Filho, A.M.; Sobaih, B.H.; Sobhani, S.; Sobngwi, E.; Soneji, S.S.; Soofi, M.; Soosaraei, M.; Sorensen, R.J.D.; Soriano, J.B.; Soyiri, I.N.; Sposato, L.A.; Sreeramareddy, C.T.; Srinivasan, V.; Stanaway, J.D.; Stein, D.J.; Steiner, C.; Steiner, T.J.; Stokes, M.A.; Stovner, L.J.; Subart, M.L.; Sudaryanto, A.; Sufiyan, M.B.; Sunguya, B.F.; Sur, P.J.; Sutradhar, I.; Sykes, B.L.; Sylte, D.O.; Tabarés-Seisdedos, R.; Tadakamadla, S.K.; Tadesse, B.T.; Tandon, N.; Tassew, S.G.; Tavakkoli, M.; Taveira, N.; Taylor, H.R.; Tehrani-Banihashemi, A.; Tekalign, T.G.; Tekelemedhin, S.W.; Tekle, M.G.; Temesgen, H.; Temsah, M-H.; Temsah, O.; Terkawi, A.S.; Teweldemedhin, M.; Thankappan, K.R.; Thomas, N.; Tilahun, B.; To, Q.G.; Tonelli, M.; Topor-Madry, R.; Topouzis, F.; Torre, A.E.; Tortajada-Girbés, M.; Touvier, M.; Tovani-Palone, M.R.; Towbin, J.A.; Tran, B.X.; Tran, K.B.; Troeger, C.E.; Truelsen, T.C.; Tsilimbaris, M.K.; Tsoi, D.; Tudor Car, L.; Tuzcu, E.M.; Ukwaja, K.N.; Ullah, I.; Undurraga, E.A.; Unutzer, J.; Updike, R.L.; Usman, M.S.; Uthman, O.A.; Vaduganathan, M.; Vaezi, A.; Valdez, P.R.; Varughese, S.; Vasankari, T.J.; Venketasubramanian, N.; Villafaina, S.; Violante, F.S.; Vladimirov, S.K.; Vlassov, V.; Vollset, S.E.; Vosoughi, K.; Vujcic, I.S.; Wagnew, F.S.; Waheed, Y.; Waller, S.G.; Wang, Y.; Wang, Y-P.; Weiderpass, E.; Weintraub, R.G.; Weiss, D.J.; Weldegebreal, F.; Weldegwergs, K.G.; Werdecker, A.; West, T.E.; Whiteford, H.A.; Widecka, J.; Wijeratne, T.; Wilner, L.B.; Wilson, S.; Winkler, A.S.; Wiyeh, A.B.; Wiysonge, C.S.; Wolfe, C.D.A.; Woolf, A.D.; Wu, S.; Wu, Y-C.; Wyper, G.M.A.; Xavier, D.; Xu, G.; Yadgir, S.; Yadollahpour, A.; Yahyazadeh Jabbari, S.H.; Yamada, T.; Yan, L.L.; Yano, Y.; Yaseri, M.; Yasin, Y.J.; Yeshaneh, A.; Yimer, E.M.; Yip, P.; Yisma, E.; Yonemoto, N.; Yoon, S-J.; Yotebieng, M.; Younis, M.Z.; Yousefifard, M.; Yu, C.; Zadnik, V.; Zaidi, Z.; Zaman, S.B.; Zamani, M.; Zare, Z.; Zeleke, A.J.; Zenebe, Z.M.; Zhang, K.; Zhao, Z.; Zhou, M.; Zodpey, S.; Zucker, I.; Vos, T.; Murray, C.J.L. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2018, 392(10159), 1789-1858. doi: 10.1016/S0140-6736(18)32279-7 PMID: 30496104
  3. Villarroel, M.A.; Terlizzi, E.P. Symptoms of depression among adults: United States, 2019. NCHS Data Brief, 2020, (379), 1-8. PMID: 33054920
  4. Datta, S.; Suryadevara, U.; Cheong, J. Mood disorders. Continuum (Minneap. Minn.), 2021, 27(6), 1712-1737. doi: 10.1212/CON.0000000000001051 PMID: 34881733
  5. Scheltens, P.; De Strooper, B.; Kivipelto, M.; Holstege, H.; Chételat, G.; Teunissen, C.E.; Cummings, J.; van der Flier, W.M. Alzheimer’s disease. Lancet, 2021, 397(10284), 1577-1590. doi: 10.1016/S0140-6736(20)32205-4 PMID: 33667416
  6. Novick, D.M.; Swartz, H.A.; Frank, E. Suicide attempts in bipolar I and bipolar II disorder: A review and meta-analysis of the evidence. Bipolar Disord., 2010, 12(1), 1-9. doi: 10.1111/j.1399-5618.2009.00786.x PMID: 20148862
  7. Hasin, D.S.; Sarvet, A.L.; Meyers, J.L.; Saha, T.D.; Ruan, W.J.; Stohl, M.; Grant, B.F. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry, 2018, 75(4), 336-346. doi: 10.1001/jamapsychiatry.2017.4602 PMID: 29450462
  8. WHO. Schizophrenia. 2022.
  9. Ghneim, M.; Diaz, J.J., Jr Dementia and the critically ill older adult. Crit. Care Clin., 2021, 37(1), 191-203. doi: 10.1016/j.ccc.2020.08.010 PMID: 33190770
  10. Mitchell, S.L. Advanced dementia. N. Engl. J. Med., 2015, 372(26), 2533-2540. doi: 10.1056/NEJMcp1412652 PMID: 26107053
  11. Stępnicki, P.; Kondej, M.; Kaczor, A.A. Current concepts and treatments of schizophrenia. Molecules, 2018, 23(8), 2087. doi: 10.3390/molecules23082087 PMID: 30127324
  12. Fabbri, C.; Kasper, S.; Zohar, J.; Souery, D.; Montgomery, S.; Albani, D.; Forloni, G.; Ferentinos, P.; Rujescu, D.; Mendlewicz, J.; De Ronchi, D.; Riva, M.A.; Lewis, C.M.; Serretti, A. Drug repositioning for treatment-resistant depression: Hypotheses from a pharmacogenomic study. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2021, 104, 110050. doi: 10.1016/j.pnpbp.2020.110050 PMID: 32738352
  13. Colpo, G.D.; Leboyer, M.; Dantzer, R.; Trivedi, M.H.; Teixeira, A.L. Immune-based strategies for mood disorders: Facts and challenges. Expert Rev. Neurother., 2018, 18(2), 139-152. doi: 10.1080/14737175.2018.1407242 PMID: 29179585
  14. Paul, M.; Poyan Mehr, A.; Kreutz, R. Physiology of local renin-angiotensin systems. Physiol. Rev., 2006, 86(3), 747-803. doi: 10.1152/physrev.00036.2005 PMID: 16816138
  15. Fyhrquist, F.; Saijonmaa, O. Renin-angiotensin system revisited. J. Intern. Med., 2008, 264(3), 224-236. doi: 10.1111/j.1365-2796.2008.01981.x PMID: 18793332
  16. Simões e Silva, A.C.; Teixeira, M.M. ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis. Pharmacol. Res., 2016, 107, 154-162. doi: 10.1016/j.phrs.2016.03.018 PMID: 26995300
  17. Rodrigues Prestes, T.R.; Rocha, N.P.; Miranda, A.S.; Teixeira, A.L. Simoes-E-Silva, A.C. The anti-inflammatory potential of ACE2/Angiotensin-(1-7)/mas receptor axis: Evidence from basic and clinical research. Curr. Drug Targets, 2017, 18(11), 1301-1313. PMID: 27469342
  18. Kamo, T.; Akazawa, H.; Komuro, I. Pleiotropic effects of angiotensin II receptor signaling in cardiovascular homeostasis and aging. Int. Heart J., 2015, 56(3), 249-254. doi: 10.1536/ihj.14-429 PMID: 25912907
  19. Rocha, N.P.; Toledo, A.; Corgosinho, L.T.S.; de Souza, L.C.; Guimarães, H.C.; Resende, E.P.F.; Braz, N.F.T.; Gomes, K.B.; Simoes e Silva, A.C.; Caramelli, P.; Teixeira, A.L. Cerebrospinal fluid levels of angiotensin-converting enzyme are associated with amyloid-β42 burden in Alzheimer’s disease. J. Alzheimers Dis., 2018, 64(4), 1085-1090. doi: 10.3233/JAD-180282 PMID: 30040721
  20. Rocha, N.P.; Simoes e Silva, A.C.; Prestes, T.R.R.; Feracin, V.; Machado, C.A.; Ferreira, R.N.; Teixeira, A.L.; de Miranda, A.S. RAS in the central nervous system: Potential role in neuropsychiatric disorders. Curr. Med. Chem., 2018, 25(28), 3333-3352. doi: 10.2174/0929867325666180226102358 PMID: 29484978
  21. de Miranda, A.S.; Teixeira, A.L. Coronavirus disease-2019 conundrum: RAS blockade and geriatric-associated neuropsychiatric disorders. Front. Med. (Lausanne), 2020, 7, 515. doi: 10.3389/fmed.2020.00515 PMID: 32850927
  22. Lakatta, E.G. The reality of getting old. Nat. Rev. Cardiol., 2018, 15(9), 499-500. doi: 10.1038/s41569-018-0068-y PMID: 30065260
  23. AlGhatrif, M.; Cingolani, O.; Lakatta, E.G. The dilemma of coronavirus disease 2019, aging, and cardiovascular disease. JAMA Cardiol., 2020, 5(7), 747-748. doi: 10.1001/jamacardio.2020.1329 PMID: 32242886
  24. Lavoie, J.L.; Sigmund, C.D. Minireview: Overview of the renin-angiotensin system--an endocrine and paracrine system. Endocrinology, 2003, 144(6), 2179-2183. doi: 10.1210/en.2003-0150 PMID: 12746271
  25. Guo, D.F.; Sun, Y.L.; Hamet, P.; Inagami, T. The angiotensin II type 1 receptor and receptor-associated proteins. Cell Res., 2001, 11(3), 165-180. doi: 10.1038/sj.cr.7290083 PMID: 11642401
  26. Simões e Silva, A.C.; Flynn, J.T. The renin-angiotensin-aldosterone system in 2011: Role in hypertension and chronic kidney disease. Pediatr. Nephrol., 2012, 27(10), 1835-1845. doi: 10.1007/s00467-011-2002-y PMID: 21947887
  27. Santos, R.A.S.; Ferreira, A.J.; Simões e Silva, A.C. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis. Exp. Physiol., 2008, 93(5), 519-527. doi: 10.1113/expphysiol.2008.042002 PMID: 18310257
  28. Tipnis, S.R.; Hooper, N.M.; Hyde, R.; Karran, E.; Christie, G.; Turner, A.J. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem., 2000, 275(43), 33238-33243. doi: 10.1074/jbc.M002615200 PMID: 10924499
  29. Santos, R.A.S.; Silva, A.C.S.; Maric, C.; Silva, D.M.R.; Machado, R.P.; de Buhr, I.; Heringer-Walther, S.; Pinheiro, S.V.B.; Lopes, M.T.; Bader, M.; Mendes, E.P.; Lemos, V.S.; Campagnole-Santos, M.J.; Schultheiss, H.P.; Speth, R.; Walther, T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8258-8263. doi: 10.1073/pnas.1432869100 PMID: 12829792
  30. Saavedra, J.M. Brain angiotensin II: New developments, unanswered questions and therapeutic opportunities. Cell. Mol. Neurobiol., 2005, 25(3-4), 485-512. doi: 10.1007/s10571-005-4011-5 PMID: 16075377
  31. Braga, V.A.; Medeiros, I.A.; Ribeiro, T.P.; França-Silva, M.S.; Botelho-Ono, M.S.; Guimarães, D.D. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: Implications in neurogenic hypertension. Braz. J. Med. Biol. Res., 2011, 44(9), 871-876. doi: 10.1590/S0100-879X2011007500088 PMID: 21755262
  32. Ando, H.; Zhou, J.; Macova, M.; Imboden, H.; Saavedra, J.M. Angiotensin II AT1 receptor blockade reverses pathological hypertrophy and inflammation in brain microvessels of spontaneously hypertensive rats. Stroke, 2004, 35(7), 1726-1731. doi: 10.1161/01.STR.0000129788.26346.18 PMID: 15143297
  33. Nishimura, Y.; Ito, T.; Hoe, K.L.; Saavedra, J.M. Chronic peripheral administration of the angiotensin II AT1 receptor antagonist Candesartan blocks brain AT1 receptors. Brain Res., 2000, 871(1), 29-38. doi: 10.1016/S0006-8993(00)02377-5 PMID: 10882779
  34. Blezer, E.L.A.; Nicolay, K.; Bär, P.R.D.; Goldschmeding, R.; Jansen, G.H.; Koomans, H.A.; Joles, J.A. Enalapril prevents imminent and reduces manifest cerebral edema in stroke-prone hypertensive rats. Stroke, 1998, 29(8), 1671-1678. doi: 10.1161/01.STR.29.8.1671 PMID: 9707211
  35. Nishimura, Y.; Ito, T.; Saavedra, J.M. Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats. Stroke, 2000, 31(10), 2478-2486. doi: 10.1161/01.STR.31.10.2478 PMID: 11022082
  36. Ito, T.; Yamakawa, H.; Bregonzio, C.; Terrón, J.A.; Falcón-Neri, A.; Saavedra, J.M. Protection against ischemia and improvement of cerebral blood flow in genetically hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist. Stroke, 2002, 33(9), 2297-2303. doi: 10.1161/01.STR.0000027274.03779.F3 PMID: 12215602
  37. Yamakawa, H.; Jezova, M.; Ando, H.; Saavedra, J.M. Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition. J. Cereb. Blood Flow Metab., 2003, 23(3), 371-380. doi: 10.1097/01.WCB.0000047369.05600.03 PMID: 12621312
  38. Dahlöf, B.; Devereux, R.B.; Kjeldsen, S.E.; Julius, S.; Beevers, G.; de Faire, U.; Fyhrquist, F.; Ibsen, H.; Kristiansson, K.; Lederballe-Pedersen, O.; Lindholm, L.H.; Nieminen, M.S.; Omvik, P.; Oparil, S.; Wedel, H. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet, 2002, 359(9311), 995-1003. doi: 10.1016/S0140-6736(02)08089-3 PMID: 11937178
  39. Schrader, J.; Lüders, S.; Kulschewski, A.; Hammersen, F.; Plate, K.; Berger, J.; Zidek, W.; Dominiak, P.; Diener, H.C. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: Principal results of a prospective randomized controlled study (MOSES). Stroke, 2005, 36(6), 1218-1224. doi: 10.1161/01.STR.0000166048.35740.a9 PMID: 15879332
  40. Julius, S.; Nesbitt, S.D.; Egan, B.M.; Weber, M.A.; Michelson, E.L.; Kaciroti, N.; Black, H.R.; Grimm, R.H., Jr; Messerli, F.H.; Oparil, S.; Schork, M.A. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N. Engl. J. Med., 2006, 354(16), 1685-1697. doi: 10.1056/NEJMoa060838 PMID: 16537662
  41. Li, J.M.; Mogi, M.; Iwanami, J.; Min, L.J.; Tsukuda, K.; Sakata, A.; Fujita, T.; Iwai, M.; Horiuchi, M. Temporary pretreatment with the angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage through an increase in capillary density. Stroke, 2008, 39(7), 2029-2036. doi: 10.1161/STROKEAHA.107.503458 PMID: 18436887
  42. Schiavone, M.T.; Santos, R.A.; Brosnihan, K.B.; Khosla, M.C.; Ferrario, C.M. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc. Natl. Acad. Sci. USA, 1988, 85(11), 4095-4098. doi: 10.1073/pnas.85.11.4095 PMID: 3375255
  43. Block, C.H.; Santos, R.A.S.; Brosnihan, K.B.; Ferrario, C.M. Immunocytochemical localization of angiotensin-(1-7) in the rat forebrain. Peptides, 1988, 9(6), 1395-1401. doi: 10.1016/0196-9781(88)90208-2 PMID: 3247256
  44. Campagnole-Santos, M.J.; Heringer, S.B.; Batista, E.N.; Khosla, M.C.; Santos, R.A. Differential baroreceptor reflex modulation by centrally infused angiotensin peptides. Am. J. Physiol., 1992, 263(1 Pt 2), R89-R94. PMID: 1636797
  45. Heringer-Walther, S.; Batista, É.N.; Walther, T.; Khosla, M.C.; Santos, R.A.S.; Campagnole-Santos, M.J. Baroreflex improvement in shr after ace inhibition involves angiotensin-(1-7). Hypertension, 2001, 37(5), 1309-1314. doi: 10.1161/01.HYP.37.5.1309 PMID: 11358946
  46. Chaves, G.Z.; Caligiorne, S.M.; Santos, R.A.S.; Khosla, M.C.; Campagnole-Santos, M.J. Modulation of the baroreflex control of heart rate by angiotensin-(1-7) at the nucleus tractus solitarii of normotensive and spontaneously hypertensive rats. J. Hypertens., 2000, 18(12), 1841-1848. doi: 10.1097/00004872-200018120-00019 PMID: 11132609
  47. Yamazato, M.; Ferreira, A.J.; Yamazato, Y.; Diez-Freire, C.; Yuan, L.; Gillies, R.; Raizada, M.K. Gene transfer of angiotensin-converting enzyme 2 in the nucleus tractus solitarius improves baroreceptor heart rate reflex in spontaneously hypertensive rats. J. Renin Angiotensin Aldosterone Syst., 2011, 12(4), 456-461. doi: 10.1177/1470320311412809 PMID: 21719524
  48. Jiang, T.; Gao, L.; Shi, J.; Lu, J.; Wang, Y.; Zhang, Y. Angiotensin-(1-7) modulates renin-angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats. Pharmacol. Res., 2013, 67(1), 84-93. doi: 10.1016/j.phrs.2012.10.014 PMID: 23127917
  49. Regenhardt, R.W.; Mecca, A.P.; Desland, F.; Ritucci-Chinni, P.F.; Ludin, J.A.; Greenstein, D.; Banuelos, C.; Bizon, J.L.; Reinhard, M.K.; Sumners, C. Centrally administered angiotensin-(1-7) increases the survival of stroke-prone spontaneously hypertensive rats. Exp. Physiol., 2014, 99(2), 442-453. doi: 10.1113/expphysiol.2013.075242 PMID: 24142453
  50. Leong, D.S.; Terrón, J.A.; Falcón-Neri, A.; Armando, I.; Ito, T.; Jöhren, O.; Tonelli, L.H.; Hoe, K.L.; Saavedra, J.M. Restraint stress modulates brain, pituitary and adrenal expression of angiotensin II AT(1A), AT(1B) and AT(2) receptors. Neuroendocrinology, 2002, 75(4), 227-240. doi: 10.1159/000054714 PMID: 11979053
  51. Sapolsky, R.M. The possibility of neurotoxicity in the hippocampus in major depression: A primer on neuron death. Biol. Psychiatry, 2000, 48(8), 755-765. doi: 10.1016/S0006-3223(00)00971-9 PMID: 11063972
  52. Baghai, T.C.; Binder, E.B.; Schule, C.; Salyakina, D.; Eser, D.; Lucae, S.; Zwanzger, P.; Haberger, C.; Zill, P.; Ising, M.; Deiml, T.; Uhr, M.; Illig, T.; Wichmann, H-E.; Modell, S.; Nothdurfter, C.; Holsboer, F.; Müller-Myhsok, B.; Möller, H-J.; Rupprecht, R.; Bondy, B. Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol. Psychiatry, 2006, 11(11), 1003-1015. doi: 10.1038/sj.mp.4001884 PMID: 16924268
  53. Popoli, M.; Yan, Z.; McEwen, B.S.; Sanacora, G. The stressed synapse: The impact of stress and glucocorticoids on glutamate transmission. Nat. Rev. Neurosci., 2012, 13(1), 22-37. doi: 10.1038/nrn3138 PMID: 22127301
  54. Chetty, S.; Friedman, A.R.; Taravosh-Lahn, K.; Kirby, E.D.; Mirescu, C.; Guo, F.; Krupik, D.; Nicholas, A.; Geraghty, A.C.; Krishnamurthy, A.; Tsai, M-K.; Covarrubias, D.; Wong, A.T.; Francis, D.D.; Sapolsky, R.M.; Palmer, T.D.; Pleasure, D.; Kaufer, D. Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. Mol. Psychiatry, 2014, 19(12), 1275-1283. doi: 10.1038/mp.2013.190 PMID: 24514565
  55. Castren, E.; Saavedra, J.M. Repeated stress increases the density of angiotensin II binding sites in rat paraventricular nucleus and subfornical organ. Endocrinology, 1988, 122(1), 370-372. doi: 10.1210/endo-122-1-370 PMID: 3335214
  56. Yang, G.; Wan, Y.; Zhu, Y. Angiotensin II--an important stress hormone. Neurosignals, 1996, 5(1), 1-8. doi: 10.1159/000109168 PMID: 8739318
  57. Wincewicz, D.; Braszko, J. Validation of brain angiotensin system blockade as a novel drug target in pharmacological treatment of neuropsychiatric disorders. Pharmacopsychiatry, 2017, 50(6), 233-247. doi: 10.1055/s-0043-112345 PMID: 28641333
  58. Qadri, F.; Culman, J.; Veltmar, A.; Maas, K.; Rascher, W.; Unger, T. Angiotensin II-induced vasopressin release is mediated through alpha-1 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus. J. Pharmacol. Exp. Ther., 1993, 267(2), 567-574. PMID: 8246129
  59. Jezova, D.; Skultetyova, I.; Tokarev, D.I.; Bakos, P.; Vigas, M. Vasopressin and oxytocin in stress. Ann. N. Y. Acad. Sci., 1995, 771(1 Stress), 192-203. doi: 10.1111/j.1749-6632.1995.tb44681.x PMID: 8597399
  60. Schnider, P.; Bissantz, C.; Bruns, A.; Dolente, C.; Goetschi, E.; Jakob-Roetne, R.; Künnecke, B.; Mueggler, T.; Muster, W.; Parrott, N.; Pinard, E.; Ratni, H.; Risterucci, C.; Rogers-Evans, M.; von Kienlin, M.; Grundschober, C. Discovery of balovaptan, a vasopressin 1a receptor antagonist for the treatment of autism spectrum disorder. J. Med. Chem., 2020, 63(4), 1511-1525. doi: 10.1021/acs.jmedchem.9b01478 PMID: 31951127
  61. Saavedra, J.M.; Ando, H.; Armando, I.; Baiardi, G.; Bregonzio, C.; Jezova, M.; Zhou, J. Brain angiotensin II, an important stress hormone: Regulatory sites and therapeutic opportunities. Ann. N. Y. Acad. Sci., 2004, 1018(1), 76-84. doi: 10.1196/annals.1296.009 PMID: 15240355
  62. Khoury, N.M.; Marvar, P.J.; Gillespie, C.F.; Wingo, A.; Schwartz, A.; Bradley, B.; Kramer, M.; Ressler, K.J. The renin-angiotensin pathway in posttraumatic stress disorder: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms. J. Clin. Psychiatry, 2012, 73(6), 849-855. doi: 10.4088/JCP.11m07316 PMID: 22687631
  63. Marvar, P.J.; Goodman, J.; Fuchs, S.; Choi, D.C.; Banerjee, S.; Ressler, K.J. Angiotensin type 1 receptor inhibition enhances the extinction of fear memory. Biol. Psychiatry, 2014, 75(11), 864-872. doi: 10.1016/j.biopsych.2013.08.024 PMID: 24094510
  64. Raasch, W.; Wittmershaus, C.; Dendorfer, A.; Voges, I.; Pahlke, F.; Dodt, C.; Dominiak, P.; Jöhren, O. Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats. Endocrinology, 2006, 147(7), 3539-3546. doi: 10.1210/en.2006-0198 PMID: 16574788
  65. Augusto, M.L. Activation of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis attenuates the cardiac reactiv- ity to acute emotional stress. Am. J. Physiol. Heart Circ. Physiol., 2013, H1057-H1067.
  66. Zhu, D.; Tong, Q.; Liu, W.; Tian, M.; Xie, W.; Ji, L.; Shi, J. Angiotensin (1-7) protects against stress-induced gastric lesions in rats. Biochem. Pharmacol., 2014, 87(3), 467-476. doi: 10.1016/j.bcp.2013.10.026 PMID: 24231511
  67. Oscar, C.G.; Müller-Ribeiro, F.C.F.; de Castro, L.G.; Martins Lima, A.; Campagnole-Santos, M.J.; Santos, R.A.S.; Xavier, C.H.; Fontes, M.A.P. Angiotensin-(1-7) in the basolateral amygdala attenuates the cardiovascular response evoked by acute emotional stress. Brain Res., 2015, 1594, 183-189. doi: 10.1016/j.brainres.2014.11.006 PMID: 25446442
  68. Lazaroni, T.L.N.; Bastos, C.P.; Moraes, M.F.D.; Santos, R.S.; Pereira, G.S. Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice. Neurobiol. Learn. Mem., 2016, 127, 27-33. doi: 10.1016/j.nlm.2015.11.012 PMID: 26642920
  69. Moura Santos, D.; Ribeiro Marins, F.; Limborço-Filho, M.; de Oliveira, M.L.; Hamamoto, D.; Xavier, C.H.; Moreira, F.A.; Santos, R.A.S.; Campagnole-Santos, M.J.; Peliky Fontes, M.A. Chronic overexpression of angiotensin-(1-7) in rats reduces cardiac reactivity to acute stress and dampens anxious behavior. Stress, 2017, 20(2), 189-196. doi: 10.1080/10253890.2017.1296949 PMID: 28288545
  70. Saavedra, J.M. Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders. Clin. Sci. (Lond.), 2012, 123(10), 567-590. doi: 10.1042/CS20120078 PMID: 22827472
  71. Ren, L.; Lu, X.; Danser, A.H.J. Revisiting the brain renin-angiotensin system—focus on novel therapies. Curr. Hypertens. Rep., 2019, 21(4), 28. doi: 10.1007/s11906-019-0937-8 PMID: 30949864
  72. Gong, X.; Hu, H.; Qiao, Y.; Xu, P.; Yang, M.; Dang, R.; Han, W.; Guo, Y.; Chen, D.; Jiang, P. The involvement of renin-angiotensin system in lipopolysaccharide-induced behavioral changes, neuroinflammation, and disturbed insulin signaling. Front. Pharmacol., 2019, 10, 318. doi: 10.3389/fphar.2019.00318 PMID: 31001119
  73. Saavedra, J.M.; Sánchez-Lemus, E.; Benicky, J. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. Psychoneuroendocrinology, 2011, 36(1), 1-18. doi: 10.1016/j.psyneuen.2010.10.001 PMID: 21035950
  74. Timaru-Kast, R.; Wyschkon, S.; Luh, C.; Schaible, E.V.; Lehmann, F.; Merk, P.; Werner, C.; Engelhard, K.; Thal, S.C. Delayed inhibition of angiotensin II receptor type 1 reduces secondary brain damage and improves functional recovery after experimental brain trauma. Crit. Care Med., 2012, 40(3), 935-944. doi: 10.1097/CCM.0b013e31822f08b9 PMID: 21926585
  75. Villapol, S.; Balarezo, M.G.; Affram, K.; Saavedra, J.M.; Symes, A.J. Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Brain, 2015, 138(11), 3299-3315. doi: 10.1093/brain/awv172 PMID: 26115674
  76. Valenzuela, R.; Costa-Besada, M.A.; Iglesias-Gonzalez, J.; Perez-Costas, E.; Villar-Cheda, B.; Garrido-Gil, P.; Melendez-Ferro, M.; Soto-Otero, R.; Lanciego, J.L.; Henrion, D.; Franco, R.; Labandeira-Garcia, J.L. Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration. Cell Death Dis., 2016, 7(10), e2427. doi: 10.1038/cddis.2016.327 PMID: 27763643
  77. Hammer, A.; Stegbauer, J.; Linker, R.A. Macrophages in neuroinflammation: Role of the renin-angiotensin-system. Pflugers Arch., 2017, 469(3-4), 431-444. doi: 10.1007/s00424-017-1942-x PMID: 28190090
  78. Du, Y.C.; Xu, J.Y.; Zhang, S.J. Effects of angiotensin II receptor antagonist on expression of collagen III, collagen V, and transforming growth factor beta1 in the airway walls of sensitized rats. Chin. Med. J. (Engl.), 2004, 117(6), 908-912. PMID: 15198897
  79. Dagenais, N.J.; Jamali, F. Protective effects of angiotensin II interruption: Evidence for antiinflammatory actions. Pharmacotherapy, 2005, 25(9), 1213-1229. doi: 10.1592/phco.2005.25.9.1213 PMID: 16164395
  80. Ferrari, A.J.; Stockings, E.; Khoo, J.P.; Erskine, H.E.; Degenhardt, L.; Vos, T.; Whiteford, H.A. The prevalence and burden of bipolar disorder: Findings from the Global Burden of Disease Study 2013. Bipolar Disord., 2016, 18(5), 440-450. doi: 10.1111/bdi.12423 PMID: 27566286
  81. Liu, Q.; He, H.; Yang, J.; Feng, X.; Zhao, F.; Lyu, J. Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study. J. Psychiatr. Res., 2020, 126, 134-140. doi: 10.1016/j.jpsychires.2019.08.002 PMID: 31439359
  82. Harmer, C.J.; Duman, R.S.; Cowen, P.J. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry, 2017, 4(5), 409-418. doi: 10.1016/S2215-0366(17)30015-9 PMID: 28153641
  83. Braszko, J.J.; Karwowska-Polecka, W.; Halicka, D.; Gard, P.R. Captopril and enalapril improve cognition and depressed mood in hypertensive patients. J. Basic Clin. Physiol. Pharmacol., 2003, 14(4), 323-343. doi: 10.1515/JBCPP.2003.14.4.323 PMID: 15198305
  84. Tanaka, J.; Kariya, K.; Nomura, M. Angiotensin II reduces serotonin release in the rat subfornical organ area. Peptides, 2003, 24(6), 881-887. doi: 10.1016/S0196-9781(03)00164-5 PMID: 12948840
  85. Nasr, S.J.; Crayton, J.W.; Agarwal, B.; Wendt, B.; Kora, R. Lower frequency of antidepressant use in patients on renin-angiotensin-aldosterone system modifying medications. Cell. Mol. Neurobiol., 2011, 31(4), 615-618. doi: 10.1007/s10571-011-9656-7 PMID: 21301954
  86. Ahola, A.J.; Harjutsalo, V.; Forsblom, C.; Groop, P.H. Renin-angiotensin-aldosterone-blockade is associated with decreased use of antidepressant therapy in patients with type 1 diabetes and diabetic nephropathy. Acta Diabetol., 2014, 51(4), 529-533. doi: 10.1007/s00592-013-0547-x PMID: 24436029
  87. Ping, G.; Qian, W.; Song, G.; Zhaochun, S. Valsartan reverses depressive/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice. Pharmacol. Biochem. Behav., 2014, 124, 5-12. doi: 10.1016/j.pbb.2014.05.006 PMID: 24844704
  88. Aswar, U.; Chepurwar, S.; Shintre, S.; Aswar, M. Telmisartan attenuates diabetes induced depression in rats. Pharmacol. Rep., 2017, 69(2), 358-364. doi: 10.1016/j.pharep.2016.12.004 PMID: 28189098
  89. Ayyub, M.; Najmi, A.K.; Akhtar, M. Protective effect of irbesartan an angiotensin (AT1) receptor antagonist in unpredictable chronic mild stress induced depression in mice. Drug Res. (Stuttg.), 2017, 67(1), 59-64. PMID: 27756096
  90. Zubenko, G.S.; Nixon, R.A. Mood-elevating effect of captopril in depressed patients. Am. J. Psychiatry, 1984, 141(1), 110-111. doi: 10.1176/ajp.141.1.110 PMID: 6318579
  91. Deicken, R.F. Captopril treatment of depression. Biol. Psychiatry, 1986, 21(14), 1425-1428. doi: 10.1016/0006-3223(86)90334-3 PMID: 3539210
  92. Cohen, B.M.; Zubenko, G.S. Captopril in the treatment of recurrent major depression. J. Clin. Psychopharmacol., 1988, 8(2), 143-144. doi: 10.1097/00004714-198804000-00018 PMID: 3286687
  93. Germain, L.; Chouinard, G. Treatment of recurrent unipolar major depression with captopril. Biol. Psychiatry, 1988, 23(6), 637-641. doi: 10.1016/0006-3223(88)90010-8 PMID: 3281718
  94. Germain, L.; Chouinard, G. Captopril treatment of major depression with serial measurements of blood cortisol concentrations. Biol. Psychiatry, 1989, 25(4), 489-493. doi: 10.1016/0006-3223(89)90203-5 PMID: 2649159
  95. Pavlatou, M.G.; Mastorakos, G.; Lekakis, I.; Liatis, S.; Vamvakou, G.; Zoumakis, E.; Papassotiriou, I.; Rabavilas, A.D.; Katsilambros, N.; Chrousos, G.P. Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: Preliminary results. Stress, 2008, 11(1), 62-72. doi: 10.1080/10253890701476621 PMID: 17853061
  96. Arinami, T.; Liming, L.; Mitsushio, H.; Itokawa, M.; Hamaguchi, H.; Toru, M. An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders. Biol. Psychiatry, 1996, 40(11), 1122-1127. doi: 10.1016/S0006-3223(95)00597-8 PMID: 8931914
  97. Saab, Y.B.; Gard, P.R.; Yeoman, M.S.; Mfarrej, B.; El-Moalem, H.; Ingram, M.J. Renin-angiotensin-system gene polymorphisms and depression. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2007, 31(5), 1113-1118. doi: 10.1016/j.pnpbp.2007.04.002 PMID: 17499413
  98. Martin, P.; Massol, J.; Puech, A.J. Captopril as an antidepressant? Effects on the learned helplessness paradigm in rats. Biol. Psychiatry, 1990, 27(9), 968-974. doi: 10.1016/0006-3223(90)90034-Y PMID: 2185850
  99. Okuyama, S.; Sakagawa, T.; Sugiyama, F.; Fukamizu, A.; Murakami, K. Reduction of depressive-like behavior in mice lacking angiotensinogen. Neurosci. Lett., 1999, 261(3), 167-170. doi: 10.1016/S0304-3940(99)00002-6 PMID: 10081975
  100. Voigt, J.P.; Hörtnagl, H.; Rex, A.; van Hove, L.; Bader, M.; Fink, H. Brain angiotensin and anxiety-related behavior: The transgenic rat TGR(ASrAOGEN)680. Brain Res., 2005, 1046(1-2), 145-156. doi: 10.1016/j.brainres.2005.03.048 PMID: 15869747
  101. Kangussu, L.M.; Almeida-Santos, A.F.; Bader, M.; Alenina, N.; Fontes, M.A.P.; Santos, R.A.S.; Aguiar, D.C.; Campagnole-Santos, M.J. Angiotensin-(1-7) attenuates the anxiety and depression-like behaviors in transgenic rats with low brain angiotensinogen. Behav. Brain Res., 2013, 257, 25-30. doi: 10.1016/j.bbr.2013.09.003 PMID: 24016839
  102. Almeida-Santos, A.F.; Kangussu, L.M.; Moreira, F.A.; Santos, R.A.S.; Aguiar, D.C.; Campagnole-Santos, M.J. Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats. Clin. Sci. (Lond.), 2016, 130(14), 1247-1255. doi: 10.1042/CS20160116 PMID: 27129185
  103. Meira-Lima, I.V.; Pereira, A.C.; Mota, G.F.A.; Krieger, J.E.; Vallada, H. Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans. Neurosci. Lett., 2000, 293(2), 103-106. doi: 10.1016/S0304-3940(00)01512-3 PMID: 11027844
  104. Sanches, M.; Colpo, G.D.; Cuellar, V.A.; Bockmann, T.; Rogith, D.; Soares, J.C.; Teixeira, A.L. Decreased plasma levels of angiotensin-converting enzyme among patients with bipolar disorder. Front. Neurosci., 2021, 15, 617888. doi: 10.3389/fnins.2021.617888 PMID: 33642980
  105. de Souza Gomes, J.A.; de Souza, G.C.; Berk, M.; Cavalcante, L.M.; de Sousa, F.C.F.; Budni, J.; de Lucena, D.F.; Quevedo, J.; Carvalho, A.F.; Macêdo, D. Antimanic-like activity of candesartan in mice: Possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms. Eur. Neuropsychopharmacol., 2015, 25(11), 2086-2097. doi: 10.1016/j.euroneuro.2015.08.005 PMID: 26321203
  106. Henriksen, M.G.; Nordgaard, J.; Jansson, L.B. Genetics of schizophrenia: Overview of methods, findings and limitations. Front. Hum. Neurosci., 2017, 11, 322. doi: 10.3389/fnhum.2017.00322 PMID: 28690503
  107. Hui, L.; Wu, J.Q.; Ye, M.J.; Zheng, K.; He, J.C.; Zhang, X.; Liu, J.H.; Tian, H.J.; Gong, B.H.; Chen, D.C.; Lv, M.H.; Soares, J.C.; Zhang, X.Y. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum. Psychopharmacol., 2015, 30(2), 100-107. doi: 10.1002/hup.2460 PMID: 25694211
  108. Crescenti, A.; Gassó, P.; Mas, S.; Abellana, R.; Deulofeu, R.; Parellada, E.; Bernardo, M.; Lafuente, A. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is associated with schizophrenia in a Spanish population. Psychiatry Res., 2009, 165(1-2), 175-180. doi: 10.1016/j.psychres.2008.04.024 PMID: 18986708
  109. Gadelha, A.; Yonamine, C.M.; Nering, M.; Rizzo, L.B.; Noto, C.; Cogo-Moreira, H.; Teixeira, A.L.; Bressan, R.; Maes, M.; Brietzke, E.; Hayashi, M.A.F. Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia. Psychiatry Res., 2015, 229(3), 702-707. doi: 10.1016/j.psychres.2015.08.018 PMID: 26296754
  110. Gadelha, A.; Vendramini, A.M.; Yonamine, C.M.; Nering, M.; Berberian, A.; Suiama, M.A.; Oliveira, V.; Lima-Landman, M.T.; Breen, G.; Bressan, R.A.; Abílio, V.; Hayashi, M A F. Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia. Transl. Psychiatry, 2015, 5(12), e691. doi: 10.1038/tp.2015.181 PMID: 26645626
  111. Nani, J.V.; Dal Mas, C.; Yonamine, C.M.; Ota, V.K.; Noto, C.; Belangero, S.I.; Mari, J.J.; Bressan, R.; Cordeiro, Q.; Gadelha, A.; Hayashi, M.A.F. A study in first-episode psychosis patients: Does angiotensin I-converting enzyme (ACE) activity associated with genotype predict symptoms severity reductions after treatment with the atypical antipsychotic risperidone? Int. J. Neuropsychopharmacol., 2020, 23(11), 721-730. doi: 10.1093/ijnp/pyaa050 PMID: 32696960
  112. Mohite, S.; de Campos-Carli, S.M.; Rocha, N.P.; Sharma, S.; Miranda, A.S.; Barbosa, I.G.; Salgado, J.V.; Simoes-e-Silva, A.C.; Teixeira, A.L. Lower circulating levels of angiotensin-converting enzyme (ACE) in patients with schizophrenia. Schizophr. Res., 2018, 202, 50-54. doi: 10.1016/j.schres.2018.06.023 PMID: 29925475
  113. Chauquet, S.; Zhu, Z.; O’Donovan, M.C.; Walters, J.T.R.; Wray, N.R.; Shah, S. Association of antihypertensive drug target genes with psychiatric disorders. JAMA Psychiatry, 2021, 78(6), 623-631. doi: 10.1001/jamapsychiatry.2021.0005 PMID: 33688928
  114. Veeneman, R.R.; Vermeulen, J.M.; Abdellaoui, A.; Sanderson, E.; Wootton, R.E.; Tadros, R.; Bezzina, C.R.; Denys, D.; Munafò, M.R.; Verweij, K.J.H.; Treur, J.L. Exploring the relationship between schizophrenia and cardiovascular disease: A genetic correlation and multivariable mendelian randomization study. Schizophr. Bull., 2022, 48(2), 463-473. doi: 10.1093/schbul/sbab132 PMID: 34730178
  115. Elkahloun, A.G.; Hafko, R.; Saavedra, J.M. An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer’s disease. Alzheimers Res. Ther., 2016, 8(1), 5. doi: 10.1186/s13195-015-0167-5 PMID: 26822027
  116. Vasconcelos, G.S.; dos Santos Júnior, M.A.; Monte, A.S.; da Silva, F.E.R.; Lima, C.N.C.; Moreira, L.N. A.B.; Medeiros, I.S.; Teixeira, A.L.; de Lucena, D.F.; Vasconcelos, S.M.M.; Macedo, D.S. Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2021, 111, 110348. doi: 10.1016/j.pnpbp.2021.110348 PMID: 33984421
  117. Thakur, K.S.; Prakash, A.; Bisht, R.; Bansal, P.K. Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat. J. Renin Angiotensin Aldosterone Syst., 2015, 16(4), 917-929. doi: 10.1177/1470320313515038 PMID: 24464858
  118. Gorelick, P.B. Role of inflammation in cognitive impairment: Results of observational epidemiological studies and clinical trials. Ann. N. Y. Acad. Sci., 2010, 1207(1), 155-162. doi: 10.1111/j.1749-6632.2010.05726.x PMID: 20955439
  119. Zakrocka, I.; Targowska-Duda, K.M.; Wnorowski, A.; Kocki, T. Jóźwiak, K.; Turski, W.A.; Angiotensin, I.I. Angiotensin II type 1 receptor blockers inhibit KAT II activity in the brain—its possible clinical applications. Neurotox. Res., 2017, 32(4), 639-648. doi: 10.1007/s12640-017-9781-2 PMID: 28733707
  120. Linderholm, K.R.; Skogh, E.; Olsson, S.K.; Dahl, M.L.; Holtze, M.; Engberg, G.; Samuelsson, M.; Erhardt, S. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr. Bull., 2012, 38(3), 426-432. doi: 10.1093/schbul/sbq086 PMID: 20729465
  121. Alzheimer’s Association. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement., 2020, 2020. PMID: 32157811
  122. Alzheimer’s Association. FY19-21 strategic plan. 2019. Available from: https://www.alz.org/media/Documents/strategic-plan-fy2019-2021.pdf
  123. Selkoe, D.J. Alzheimer’s disease: Genotypes, phenotypes, and treatments. Science, 1997, 275(5300), 630-631. doi: 10.1126/science.275.5300.630 PMID: 9019820
  124. Clinton, L.K.; Blurton-Jones, M.; Myczek, K.; Trojanowski, J.Q.; LaFerla, F.M. Synergistic Interactions between Abeta, tau, and α-synuclein: Acceleration of neuropathology and cognitive decline. J. Neurosci., 2010, 30(21), 7281-7289. doi: 10.1523/JNEUROSCI.0490-10.2010 PMID: 20505094
  125. Giasson, B.I.; Lee, V.M.Y.; Trojanowski, J.Q. Interactions of amyloidogenic proteins. Neuromolecular Med., 2003, 4(1-2), 49-58. doi: 10.1385/NMM:4:1-2:49 PMID: 14528052
  126. Walker, L.; McAleese, K.E.; Thomas, A.J.; Johnson, M.; Martin-Ruiz, C.; Parker, C.; Colloby, S.J.; Jellinger, K.; Attems, J. Neuropathologically mixed Alzheimer’s and Lewy body disease: Burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathol., 2015, 129(5), 729-748. doi: 10.1007/s00401-015-1406-3 PMID: 25758940
  127. Kovacs, G.G.; Alafuzoff, I.; Al-Sarraj, S.; Arzberger, T.; Bogdanovic, N.; Capellari, S.; Ferrer, I.; Gelpi, E.; Kövari, V.; Kretzschmar, H.; Nagy, Z.; Parchi, P.; Seilhean, D.; Soininen, H.; Troakes, C.; Budka, H. Mixed brain pathologies in dementia: The BrainNet Europe consortium experience. Dement. Geriatr. Cogn. Disord., 2008, 26(4), 343-350. doi: 10.1159/000161560 PMID: 18849605
  128. Barker, W.W.; Luis, C.A.; Kashuba, A.; Luis, M.; Harwood, D.G.; Loewenstein, D.; Waters, C.; Jimison, P.; Shepherd, E.; Sevush, S.; Graff-Radford, N.; Newland, D.; Todd, M.; Miller, B.; Gold, M.; Heilman, K.; Doty, L.; Goodman, I.; Robinson, B.; Pearl, G.; Dickson, D.; Duara, R. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis. Assoc. Disord., 2002, 16(4), 203-212. doi: 10.1097/00002093-200210000-00001 PMID: 12468894
  129. Buchhave, P.; Minthon, L.; Zetterberg, H.; Wallin, A.K.; Blennow, K.; Hansson, O. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch. Gen. Psychiatry, 2012, 69(1), 98-106. doi: 10.1001/archgenpsychiatry.2011.155 PMID: 22213792
  130. Braak, E.; Griffing, K.; Arai, K.; Bohl, J.; Bratzke, H.; Braak, H. Neuropathology of Alzheimer’s disease: What is new since A. Alzheimer? Eur. Arch. Psychiatry Clin. Neurosci., 1999, 249(Suppl. 3), 14-22.
  131. dos Santos Picanco, L.C.; Ozela, P.F.; de Fatima de Brito Brito, M.; Pinheiro, A.A.; Padilha, E.C.; Braga, F.S.; de Paula da Silva, C.H.T.; dos Santos, C.B.R.; Rosa, J.M.C.; da Silva Hage-Melim, L.I. Alzheimer’s disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment. Curr. Med. Chem., 2018, 25(26), 3141-3159. doi: 10.2174/0929867323666161213101126 PMID: 30191777
  132. Wright, J.W.; Harding, J.W. The brain renin-angiotensin system: A diversity of functions and implications for CNS diseases. Pflugers Arch., 2013, 465(1), 133-151. doi: 10.1007/s00424-012-1102-2 PMID: 22535332
  133. Baltatu, O.C.; Campos, L.A.; Bader, M. Local renin-angiotensin system and the brain—A continuous quest for knowledge. Peptides, 2011, 32(5), 1083-1086. doi: 10.1016/j.peptides.2011.02.008 PMID: 21333703
  134. Jiang, T.; Zhang, Y.D.; Zhou, J.S.; Zhu, X.C.; Tian, Y.Y.; Zhao, H.D.; Lu, H.; Gao, Q.; Tan, L.; Yu, J.T. Angiotensin-(1-7) is reduced and inversely correlates with Tau hyperphosphorylation in animal models of Alzheimer’s disease. Mol. Neurobiol., 2016, 53(4), 2489-2497. doi: 10.1007/s12035-015-9260-9 PMID: 26044748
  135. Kehoe, P.G.; Wong, S.; Mulhim, A.L. N.; Palmer, L.E.; Miners, J.S. Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology. Alzheimers Res. Ther., 2016, 8(1), 50. doi: 10.1186/s13195-016-0217-7 PMID: 27884212
  136. Jiang, T.; Tan, L.; Gao, Q.; Lu, H.; Zhu, X.C.; Zhou, J.S.; Zhang, Y.D. Plasma Angiotensin-(1-7) is a potential biomarker for Alzheimer’s disease. Curr. Neurovasc. Res., 2016, 13(2), 96-99. doi: 10.2174/1567202613666160224124739 PMID: 26907614
  137. Ribeiro, V.T.; Cordeiro, T.M.; Filha, R.S.; Perez, L.G.; Caramelli, P.; Teixeira, A.L.; de Souza, L.C.; Simões e Silva, A.C. Circulating angiotensin-(1-7) is reduced in Alzheimer’s disease patients and correlates with white matter abnormalities: Results from a pilot study. Front. Neurosci., 2021, 15, 636754. doi: 10.3389/fnins.2021.636754 PMID: 33897352
  138. Kurata, T.; Lukic, V.; Kozuki, M.; Wada, D.; Miyazaki, K.; Morimoto, N.; Ohta, Y.; Deguchi, K.; Yamashita, T.; Hishikawa, N.; Matsuzono, K.; Ikeda, Y.; Kamiya, T.; Abe, K. Long-term effect of telmisartan on Alzheimer’s amyloid genesis in SHR-SR after tMCAO. Transl. Stroke Res., 2015, 6(2), 107-115. doi: 10.1007/s12975-013-0321-y PMID: 24435631
  139. Braszko, J.J.; Wincewicz, D.; Jakubów, P. Candesartan prevents impairment of recall caused by repeated stress in rats. Psychopharmacology (Berl.), 2013, 225(2), 421-428. doi: 10.1007/s00213-012-2829-3 PMID: 22890474
  140. Wincewicz, D.; Braszko, J.J. Telmisartan attenuates cognitive impairment caused by chronic stress in rats. Pharmacol. Rep., 2014, 66(3), 436-441. doi: 10.1016/j.pharep.2013.11.002 PMID: 24905520
  141. Wincewicz, D.; Braszko, J.J. Angiotensin II AT1 receptor blockade by telmisartan reduces impairment of spatial maze performance induced by both acute and chronic stress. J. Renin Angiotensin Aldosterone Syst., 2015, 16(3), 495-505. doi: 10.1177/1470320314526269 PMID: 24622157
  142. Wincewicz, D.; Juchniewicz, A.; Waszkiewicz, N.; Braszko, J.J. Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced impairment of memory via HPA axis deactivation and up-regulation of brain-derived neurotrophic factor gene expression. Pharmacol. Biochem. Behav., 2016, 148, 108-118. doi: 10.1016/j.pbb.2016.06.010 PMID: 27375198
  143. Li, N.C.; Lee, A.; Whitmer, R.A.; Kivipelto, M.; Lawler, E.; Kazis, L.E.; Wolozin, B. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: Prospective cohort analysis. BMJ, 2010, 340(jan12 1), b5465. doi: 10.1136/bmj.b5465 PMID: 20068258
  144. Kume, K.; Hanyu, H.; Sakurai, H.; Takada, Y.; Onuma, T.; Iwamoto, T. Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer’s disease. Geriatr. Gerontol. Int., 2012, 12(2), 207-214. doi: 10.1111/j.1447-0594.2011.00746.x PMID: 21929736
  145. Zhuang, S.; Wang, H.F.; Wang, X.; Li, J.; Xing, C.M. The association of renin-angiotensin system blockade use with the risks of cognitive impairment of aging and Alzheimer’s disease: A meta-analysis. J. Clin. Neurosci., 2016, 33, 32-38. doi: 10.1016/j.jocn.2016.02.036 PMID: 27475317
  146. Uekawa, K.; Hasegawa, Y.; Senju, S.; Nakagata, N.; Ma, M.; Nakagawa, T.; Koibuchi, N.; Kim-Mitsuyama, S. Intracerebroventricular infusion of angiotensin-(1-7) ameliorates cognitive impairment and memory dysfunction in a mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2016, 53(1), 127-133. doi: 10.3233/JAD-150642 PMID: 27128367
  147. Chen, J.L.; Zhang, D.L.; Sun, Y.; Zhao, Y.X.; Zhao, K.X.; Pu, D.; Xiao, Q. Angiotensin-(1-7) administration attenuates Alzheimer’s disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation. Neuroscience, 2017, 346, 267-277. doi: 10.1016/j.neuroscience.2017.01.027 PMID: 28147245
  148. Varshney, V.; Garabadu, D. Ang (1-7)/Mas receptor-axis activation promotes amyloid beta-induced altered mitochondrial bioenergetics in discrete brain regions of Alzheimer’s disease-like rats. Neuropeptides, 2021, 86, 102122. doi: 10.1016/j.npep.2021.102122 PMID: 33508525
  149. Duan, R. Wang, S.Y.; Wei, B.; Deng, Y.; Fu, X.X.; Gong, P.Y.; e, Y.; Sun, X.J.; Cao, H.M.; Shi, J.Q.; Jiang, T.; Zhang, Y.D. Angiotensin-(1-7) analogue AVE0991 modulates astrocyte-mediated neuroinflammation via lncRNA SNHG14/miR-223-3p/NLRP3 pathway and offers neuroprotection in a transgenic mouse model of Alzheimer’s disease. J. Inflamm. Res., 2021, 14, 7007-7019. doi: 10.2147/JIR.S343575 PMID: 34955647
  150. Evans, C.E.; Miners, J.S.; Piva, G.; Willis, C.L.; Heard, D.M.; Kidd, E.J.; Good, M.A.; Kehoe, P.G. ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease. Acta Neuropathol., 2020, 139(3), 485-502. doi: 10.1007/s00401-019-02098-6 PMID: 31982938
  151. Arendse, L.B.; Danser, A.H.J.; Poglitsch, M.; Touyz, R.M.; Burnett, J.C., Jr; Llorens-Cortes, C.; Ehlers, M.R.; Sturrock, E.D. Novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure. Pharmacol. Rev., 2019, 71(4), 539-570. doi: 10.1124/pr.118.017129 PMID: 31537750
  152. Treiber, K.A.; Lyketsos, C.G.; Corcoran, C.; Steinberg, M.; Norton, M.; Green, R.C.; Rabins, P.; Stein, D.M.; Welsh-Bohmer, K.A.; Breitner, J.C.S.; Tschanz, J.T. Vascular factors and risk for neuropsychiatric symptoms in Alzheimer’s disease: The Cache County Study. Int. Psychogeriatr., 2008, 20(3), 538-553. doi: 10.1017/S1041610208006704 PMID: 18289451
  153. Robinson, R.G.; Jorge, R.E. Post-stroke depression: A review. Am. J. Psychiatry, 2016, 173(3), 221-231. doi: 10.1176/appi.ajp.2015.15030363 PMID: 26684921
  154. Jellinger, K.A. Pathomechanisms of vascular depression in older adults. Int. J. Mol. Sci., 2021, 23(1), 308. doi: 10.3390/ijms23010308 PMID: 35008732
  155. Machado-Silva, A.; Passos-Silva, D.; Santos, R.A.; Sinisterra, R.D. Therapeutic uses for angiotensin-(1-7). Expert Opin. Ther. Pat., 2016, 26(6), 669-678.
  156. Mogi, M.; Horiuchi, M. Effect of angiotensin II type 2 receptor on stroke, cognitive impairment and neurodegenerative diseases. Geriatr. Gerontol. Int., 2013, 13(1), 13-18. doi: 10.1111/j.1447-0594.2012.00900.x PMID: 22726823
  157. Ahmed, H.A.; Ismael, S.; Salman, M.; Devlin, P.; McDonald, M.P.; Liao, F.F.; Ishrat, T. Direct AT2R stimulation slows post-stroke cognitive decline in the 5XFAD Alzheimer’s disease mice. Mol. Neurobiol., 2022, 59(7), 4124-4140. doi: 10.1007/s12035-022-02839-x PMID: 35486224
  158. Eldahshan, W.; Sayed, M.A.; Awad, M.E.; Ahmed, H.A.; Gillis, E.; Althomali, W.; Pillai, B.; Alshammari, A.; Jackson, L.; Dong, G.; Sullivan, J.C.; Cooley, M.A.; Elsalanty, M.; Ergul, A.; Fagan, S.C. Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke. Vascul. Pharmacol., 2021, 141, 106904. doi: 10.1016/j.vph.2021.106904 PMID: 34481068
  159. Royea, J.; Lacalle-Aurioles, M.; Trigiani, L.J.; Fermigier, A.; Hamel, E. AT2R’s (Angiotensin II Type 2 Receptor’s) role in cognitive and cerebrovascular deficits in a mouse model of Alzheimer disease. Hypertension, 2020, 75(6), 1464-1474. doi: 10.1161/HYPERTENSIONAHA.119.14431 PMID: 32362228
  160. Min, L.J.; Iwanami, J.; Shudou, M.; Bai, H.Y.; Shan, B.S.; Higaki, A.; Mogi, M.; Horiuchi, M. Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion—possible amelioration of cognitive function by AT2 receptor activation. J. Neuroinflammation, 2020, 17(1), 106. doi: 10.1186/s12974-020-01775-8 PMID: 32264971
  161. Iwanami, J.; Mogi, M.; Tsukuda, K.; Wang, X.L.; Nakaoka, H.; Kan-no, H.; Chisaka, T.; Bai, H.Y.; Shan, B.S.; Kukida, M.; Horiuchi, M. Direct angiotensin II type 2 receptor stimulation by compound 21 prevents vascular dementia. J. Am. Soc. Hypertens., 2015, 9(4), 250-256. doi: 10.1016/j.jash.2015.01.010 PMID: 25753301
  162. Higaki, A.; Mogi, M.; Iwanami, J.; Min, L.J.; Bai, H.Y.; Shan, B.S.; Kukida, M.; Yamauchi, T.; Tsukuda, K.; Kan-no, H.; Ikeda, S.; Higaki, J.; Horiuchi, M. Beneficial effect of mas receptor deficiency on vascular cognitive impairment in the presence of angiotensin II type 2 receptor. J. Am. Heart Assoc., 2018, 7(3), e008121. doi: 10.1161/JAHA.117.008121 PMID: 29431106
  163. Bosnyak, S.; Jones, E.S.; Christopoulos, A.; Aguilar, M.I.; Thomas, W.G.; Widdop, R.E. Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin. Sci. (Lond.), 2011, 121(7), 297-303. doi: 10.1042/CS20110036 PMID: 21542804

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bentham Science Publishers, 2024