Paraquat and Parkinsons Disease: The Molecular Crosstalk of Upstream Signal Transduction Pathways Leading to Apoptosis
- Authors: Chung See W.1, Naidu R.1, Tang K.2
-
Affiliations:
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia
- School of Pharmacy, Monash University Malaysia
- Issue: Vol 22, No 1 (2024)
- Pages: 140-151
- Section: Neurology
- URL: https://rjpbr.com/1570-159X/article/view/644258
- DOI: https://doi.org/10.2174/1570159X21666230126161524
- ID: 644258
Cite item
Full Text
Abstract
Parkinsons disease (PD) is a heterogeneous disease involving a complex interaction between genes and the environment that affects various cellular pathways and neural networks. Several studies have suggested that environmental factors such as exposure to herbicides, pesticides, heavy metals, and other organic pollutants are significant risk factors for the development of PD. Among the herbicides, paraquat has been commonly used, although it has been banned in many countries due to its acute toxicity. Although the direct causational relationship between paraquat exposure and PD has not been established, paraquat has been demonstrated to cause the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The underlying mechanisms of the dopaminergic lesion are primarily driven by the generation of reactive oxygen species, decrease in antioxidant enzyme levels, neuroinflammation, mitochondrial dysfunction, and ER stress, leading to a cascade of molecular crosstalks that result in the initiation of apoptosis. This review critically analyses the crucial upstream molecular pathways of the apoptotic cascade involved in paraquat neurotoxicity, including mitogenactivated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT, mammalian target of rapamycin (mTOR), and Wnt/β-catenin signaling pathways.
About the authors
Wesley Chung See
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia
Email: info@benthamscience.net
Rakesh Naidu
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia
Email: info@benthamscience.net
Kim Tang
School of Pharmacy, Monash University Malaysia
Author for correspondence.
Email: info@benthamscience.net
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