Title:Paraquat and Parkinson’s Disease: The Molecular Crosstalk of Upstream
Signal Transduction Pathways Leading to Apoptosis
Volume: 22
Issue: 1
Author(s): Wesley Zhi Chung See, Rakesh Naidu and Kim San Tang*
Affiliation:
- School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia
Keywords:
Apoptosis, catenins, mitogen-activated protein kinases, paraquat, Parkinson’s disease, phosphatidylinositol 3-kinase, proto-oncogene proteins c-akt, TOR serine-threonine kinases.
Abstract: Parkinson’s 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.