Trichloroethylene Exposure and Parkinson's Disease: Environmental Risk, Metabolic Pathways, and Mechanistic Insights.

Abstract

Trichloroethylene (TCE) is a widely used industrial solvent noted for its environmental persistence and unique metabolic profile. In recent years, a growing body of epidemiological research and experimental models has implicated TCE exposure as a potential environmental risk factor in the development of Parkinson's disease (PD). TCE undergoes biotransformation primarily via cytochrome P450-mediated oxidation and glutathione conjugation. These pathways generate reactive metabolites capable of disrupting mitochondrial function, inducing oxidative stress, and activating neuroinflammatory cascades. These mechanisms are thought to contribute to the selective degeneration of dopaminergic neurons in the substantia nigra-a hallmark of PD. This review systematically evaluates the literature concerning the environmental distribution, metabolic fate, and exposure routes of TCE. It also synthesizes current evidence linking TCE-induced neurotoxicity to the pathogenesis of PD. Particular emphasis is placed on several key mechanistic insights, including α-synuclein aggregation, inhibition of mitochondrial complex I, and the roles of oxidative damage and neuroinflammation, offering a comprehensive perspective on the potential role of TCE in PD development. Moreover, the review addresses the methodological challenges associated with quantifying chronic low-level TCE exposure in human populations and underscores the need for long-term cohort studies to better assess the associated neurotoxic risks.