Environmental toxicant exposure and Parkinson’s disease: LRRK2 and inflammatory processes

Abstract

Parkinson's disease (PD) results from the progressive loss of dopamine producing neurons in the Substantia Nigra pars comapcta (SNc). This loss is thought to occur over several years to decades and current evidence suggests that neuroinflammation may play a central role in this loss. Numerous epidemiological studies have implicated chronic exposure to environmental toxicants such as heavy metals and pesticides to risk of developing PD. Indeed, many of these risk factors have been validated as rodent models of PD, able to induce dopaminergic cell loss in the SNc as well as motor dysfunction. While research strongly supports a role for environmental toxicants and inflammation in PD relatively little work has examined the interactions between these toxicants and other risk factors including senescence, genetic vulnerabilities, the gut microbiota or iii This thesis is based upon the following four manuscripts referred to in text by their corresponding chapter numbers.