Uncovering the Molecular Link Between Lead Toxicity and Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions around the world. The etiology of PD remains unknown, but environmental and occupational exposures to heavy metals are likely at play, and may impact the severity of the disease. Lead is a toxin known to affect many organs in the body throughout life, particularly the central nervous system. In this study, we summarize and examine the evidence for such environmental and/or occupational exposures, with a focus on the molecular mechanisms associated with lead exposure and its potential contribution to the onset of parkinsonism in PD. In particular, populational studies suggest higher bone and blood lead levels are associated with increased risk of PD. Interestingly, low levels of lead exposure in the very early stages of life cause increase the production of alpha-synuclein protein in animal models. Although the specific mechanisms underlying this association have not been fully assessed, oxidative stress and mitochondrial dysfunction are likely implicated and may explain the toxic effects that connect lead exposure to parkinsonism. Additional pre-clinical and clinical studies should be performed in order to further document the molecular link between lead toxicity and PD, as this may open novel perspectives in terms of disease prevention. 39, 321-335.