Environmental Substances Associated with Neurodegeneration: An Overview of Parkinson's Disease and Related Genotoxic...

Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by age, genetic predispositions, and environmental exposures, with a growing global incidence. This review aims to summarize findings from ATSDR Toxicological Profiles, EPA Risk Assessments, and other sources of peer-reviewed literature to examine the potential associations between PD and select metals, pesticides, and chlorinated organic compounds. Additionally, it explores using computational toxicology methods to elucidate the interactions between specific chemicals, associated genes, and their possible roles in PD. A total of 29 substances were identified to be neurotoxic with direct or probable association with PD. Risk of disease onset or symptom exacerbation of PD has been linked to exposures to neurodegenerative metals, pesticides, chlorinated organic compounds, and other environmental toxicants, alongside intrinsic factors such as genetic predisposition and aging. Supporting evidence from neurotoxicological studies directly or possibly associated with PD are summarized in referenced toxicological profiles and EPA risk assessments. Genotoxic endpoints evaluated in exposure-induced neurodegeneration including oxidative stress, DNA strand breaks, mitochondrial dysfunction, impaired DNA repair, and telomere alterations may play a critical role in linking environmental exposures to PD pathogenesis. Although these endpoints represent imperative data gaps between environmental and genetic risk factors for PD, isolating individual substances may not be necessary for prevention, as many co-occur at contaminated sites or within certain occupations. Further research is needed to clarify causal relationships between environmental exposure and genotoxic endpoints seen in neurodegenerative processes that can also be seen in PD for consideration in the development of preventive and therapeutic strategies.