Environmental factors in PD development Sample Clauses

Environmental factors in PD development. The first discovery, in the 1980s, that PD-like symptoms and SNpc degeneration can be caused by compounds originating outside of the body triggered a substantial paradigm shift, as scientists became aware of the fact that PD development can be influenced by environmental factors. 1-methyl-4-phenyl-tetrahydropyridine (MPTP) was discovered after illicit drug users injected themselves with a 1-methyl-4- propionoxypyridine solution that had become contaminated with MPTP during synthesis (Xxxxxxxx et al. 1983). The drug users rapidly developed parkinsonian symptoms which were later attributed to MPTP’s active metabolite MPP+ (Xxxxxxxx et al. 1984). Since then, pesticides in particular have been investigated as potentially causative agents in PD (Xxxxxxxxxx et al. 2011). While it has been difficult to fully determine which pesticides are involved in PD or indeed the disease-specific role of pesticides in general, they are generally considered to contribute to PD development (Xxxxxxxxxx et al. 2011, Kamel 2013). A recent meta-analysis concluded that exposure to pesticides was, indeed, a risk factor for PD but that a dearth of high- quality studies prevented a cause-and-effect relationship from being confirmed (Xxxxxxx & Cereda 2013). Furthermore, future studies should focus on specific pesticides, rather than pesticide use in general, to elucidate which individual compounds are involved. The meta-analysis specifically implicated paraquat and maneb as pesticides directly associated with PD. In addition to paraquat and maneb, rotenone, a pesticide often used experimentally in both in vitro and in vivo models of PD, has recently been associated with PD in a study of agricultural workers (Xxxxxx et al. 2011). While all have been implicated in PD, the 3 pesticides mentioned above have different mechanisms of action. Xxxxxxxx, like MPP+, is an inhibitor of mitochondrial CxI and causes a reduction in ATP and also increases the production of ROS (Xxxxxx et al. 2011). When used experimentally rotenone has been shown to cause PD-like symptoms in vivo (Xxxxxxx et al. 2013). Paraquat, which also causes PD-like toxicity in vivo (Xxxxxxx et al. 2013) is another mediator of ROS production but exerts its toxicity by facilitating the movement of electrons towards molecular oxygen, producing O2•- (Bus & Xxxxxx 1984). The precise mechanism of maneb toxicity is unclear although it appears to disrupt the activity of proteins containing thiol groups (Xxxxx & Xxxxx 2014) and was found ...