Neurosteroids and their Therapeutic Potential: Remembering the Contribution of Dr. Sabina Luchetti, Netherlands Institute for Neuroscience, Amsterdam, Netherlands


Cite item

Full Text

Abstract

This article traces the career of Dr. Sabina Luchetti (1969–2021), a noted physician (medical doctor, specialized in Neurology at Tor Vergata University of Rome, Italy), a dedicated neuroscientist (Ph.D. in Neuroscience at Tor Vergata University and IRCCS Santa Lucia of Rome), and a member of a renowned Netherlands group (senior researcher at Professor Swaab Laboratory of the Netherlands Institute for Neuroscience, Amsterdam, Netherlands), working in the field of brain function and diseases. She is particularly involved in the study of natural compounds, such as neurosteroids and their biosynthetic pathways in neurodegenerative and neuroinflammation- related disorders, working on post-mortem human brains.

:This editorial outlines Dr. Luchetti's wide range of interests, discloses her superior fund of knowledge, and recollects her humanitarian spirit, all of which contribute to creating a great sense of belonging to any group of researchers whom she worked with. The impact of Dr. Luchetti's work will continue to be felt for many years.

:From the bench to the bedside, her work has indirectly contributed to shedding light on the neurosteroids’ potential therapeutic effects, considering that neurosteroids and their analogues (some of which are over-the-counter) are now used to treat depression, epilepsy, and substance abuse disorders. Moreover, the potential therapeutic effects of allopregnanolone with respect to its capability to promote neuroregeneration and neuroprotection are a promising basis for future treatment of neurodegenerative diseases.

About the authors

Flavia di Michele

Mental Health Department, Rm3

Author for correspondence.
Email: info@benthamscience.net

References

  1. Baulieu, É.É. Neurosteroids: A new function in the brain. Biol. Cell, 1991, 71(1-2), 3-10. doi: 10.1016/0248-4900(91)90045-O PMID: 1912947
  2. Luchetti, S.; Huitinga, I.; Swaab, D.F. Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuroscience, 2011, 191, 6-21. doi: 10.1016/j.neuroscience.2011.04.010 PMID: 21514366
  3. Uzunova, V.; Sheline, Y.; Davis, J.M.; Rasmusson, A.; Uzunov, D.P.; Costa, E.; Guidotti, A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc. Natl. Acad. Sci., 1998, 95(6), 3239-3244. doi: 10.1073/pnas.95.6.3239 PMID: 9501247
  4. Wang, J.M.; Singh, C.; Liu, L.; Irwin, R.W.; Chen, S.; Chung, E.J.; Thompson, R.F.; Brinton, R.D. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci., 2010, 107(14), 6498-6503. doi: 10.1073/pnas.1001422107 PMID: 20231471
  5. Qi, X.R.; Luchetti, S.; Verwer, R.W.H.; Sluiter, A.A.; Mason, M.R.J.; Zhou, J.N.; Swaab, D.F. Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post-mortem study. Brain Pathol., 2018, 28(4), 536-547. doi: 10.1111/bpa.12548 PMID: 28752602
  6. Qi, X.R.; Zhao, J.; Liu, J.; Fang, H.; Swaab, D.F.; Zhou, J.N. Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders. Cereb. Cortex, 2015, 25(1), 75-83. doi: 10.1093/cercor/bht203 PMID: 23960204
  7. Luchetti, S.; Bossers, K.; Van de Bilt, S.; Agrapart, V.; Morales, R.R.; Frajese, G.V.; Swaab, D.F. Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer’s disease. Neurobiol. Aging, 2011, 32(11), 1964-1976. doi: 10.1016/j.neurobiolaging.2009.12.014 PMID: 20045216
  8. Luchetti, S.; van Eden, C.G.; Schuurman, K.; van Strien, M.E.; Swaab, D.F.; Huitinga, I. Gender differences in multiple sclerosis: Induction of estrogen signaling in male and progesterone signaling in female lesions. J. Neuropathol. Exp. Neurol., 2014, 73(2), 123-135. doi: 10.1097/NEN.0000000000000037 PMID: 24423637
  9. Luchetti, S.; Fransen, N.L.; van Eden, C.G.; Ramaglia, V.; Mason, M.; Huitinga, I. Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: A retrospective autopsy cohort analysis. Acta Neuropathol., 2018, 135(4), 511-528. doi: 10.1007/s00401-018-1818-y PMID: 29441412
  10. Luchetti, S.; Bossers, K.; Frajese, G.V.; Swaab, D.F. Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson’s disease. Brain Pathol., 2010, 20(5), 945-951. doi: 10.1111/j.1750-3639.2010.00396.x PMID: 20406233
  11. Luchetti, S.; Liere, P.; Pianos, A.; Verwer, R.W.H.; Sluiter, A.; Huitinga, I.; Schumacher, M.; Swaab, D.F.; Mason, M.R.J. Disease stage-dependent changes in brain levels and neuroprotective effects of neuroactive steroids in Parkinson’s disease. Neurobiol. Dis., 2023, 183, 106169. doi: 10.1016/j.nbd.2023.106169 PMID: 37257664
  12. Fang, Q.; Xicoy, H.; Shen, J.; Luchetti, S.; Dai, D.; Zhou, P.; Qi, X.R.; Martens, G.J.M.; Huitinga, I.; Swaab, D.F.; Liu, C.; Shan, L. Histamine-4 receptor antagonist ameliorates Parkinson-like pathology in the striatum. Brain Behav. Immun., 2021, 92, 127-138. doi: 10.1016/j.bbi.2020.11.036 PMID: 33249171
  13. Zhao, J.; Bao, A.M.; Qi, X.R.; Kamphuis, W.; Luchetti, S.; Lou, J.S.; Swaab, D.F. Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of non-suicidal elderly depressed patients. J. Affect. Disord., 2012, 138(3), 494-502. doi: 10.1016/j.jad.2012.01.013 PMID: 22357337
  14. Luchetti, S.; di Michele, F.; Romeo, E.; Brusa, L.; Bernardi, G.; Cummings, B.J.; Longone, P. Comparative non-radioactive RT-PCR assay: An approach to study the neurosteroids biosynthetic pathway in humans. J. Neurosci. Methods, 2006, 153(2), 290-298. doi: 10.1016/j.jneumeth.2005.11.005 PMID: 16378642
  15. Qi, X.R.; Verwer, R.W.H.; Bao, A.M.; Balesar, R.A.; Luchetti, S.; Zhou, J.N.; Swaab, D.F. Human brain slice culture: A useful tool to study brain disorders and potential therapeutic compounds. Neurosci. Bull., 2019, 35(2), 244-252. doi: 10.1007/s12264-018-0328-1 PMID: 30604279

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers