The neurotoxicity of pesticides: Implications for Parkinson's disease

Abstract

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder worldwide, and no effective cure is currently available. Neuropathologically, PD is characterized by the selective degeneration of dopaminergic neurons in the substantia nigra and by the accumulation of alpha-synuclein (aSyn)-rich proteinaceous inclusions within surviving neurons. As a multifactorial disorder, approximately 85 % of PD cases are sporadic with unknown etiology. Among the many risk factors implicated in PD, exposure to neurotoxic pesticides stands out as a significant contributor. While the effects of many are still uncharacterized, it has already been shown that rotenone, paraquat, maneb, and dieldrin affect critical cellular pathways, including mitochondrial and proteasomal dysfunction, aSyn aggregation, autophagy dysregulation, and disruption of dopamine metabolism. With the constant rise in pesticide usage to meet the demands of a growing human population, the risk of environmental contamination and subsequent PD development is also increasing. This review explores the molecular mechanisms by which pesticide exposure influences PD development, shedding light on their role in the pathogenesis of PD and highlighting the need for preventative measures and regulatory oversight to mitigate these risks.