The Search for Environmental Causes of Parkinson’s Disease: Moving Forward

Abstract

It is widely believed that environmental exposures contribute to the vast majority of late-onset sporadic Parkinson's disease (PD), alone or via interactions with genetic factors. The search for environmental causes of PD has however been hampered by lack of understanding the prodromal phase of PD development and the difficulties in exposure assessment during this prolonged period. On the other hand, the existence of this prodromal period, along with an increasingly better understanding of PD prodromal symptoms, provides an exciting opportunity to identify environmental factors that initiate PD pathogenesis and/or modify its progression. For prevention efforts, this prodromal stage is of a major interest. Targeting factors that enter the body via the nose or gut has become even more important since the discovery of ␣-synuclein aggregates in the enteric and olfactory nervous systems. In this paper, we speculate about novel research hypotheses and approaches that may help us better define the role of environment in PD etiology, especially during its extended and complex prodromal phase.

Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery

“…It is widely believed that environmental exposures contribute to the vast majority of sporadic Alzheimer’s, Parkinson’s, Huntington’s and prion diseases alone or via interactions with genetic factors [45,46,47,48,49]. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders [46].…”

“…Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders [46]. Proven and potential neurotoxic substances include heavy metals, organic solvents, persistent organic pollutants, plastic exudates, pesticides, brominated flame retardants, and polycyclic aromatic hydrocarbons [45,50,51,52,53,54]. Smoking is implicated in a decreased risk of developing Parkinson’s disease [45,53] and caffeinated coffee consumption is associated with a reduced risk of PD and AD [55], but this association is controversial.…”

“…Proven and potential neurotoxic substances include heavy metals, organic solvents, persistent organic pollutants, plastic exudates, pesticides, brominated flame retardants, and polycyclic aromatic hydrocarbons [45,50,51,52,53,54]. Smoking is implicated in a decreased risk of developing Parkinson’s disease [45,53] and caffeinated coffee consumption is associated with a reduced risk of PD and AD [55], but this association is controversial. According to recent discoveries, the PD patients are less likely to establish smoking habits, because of a decreased responsiveness to nicotine and that ease of smoking cessation is an early manifestation of premotor PD related to the loss of nicotinic rewards [56].…”

“…Various environmental stresses may impact amyloids and prions via different mechanisms; therefore, studying the environmental triggers and modifiers of neurodegenerative diseases is critically important. In contrast to genetic factors, environmental factors potentially could be modified, and this may have a dramatic effect on prevention, occurrence and treatment [45]. Yeast model systems described below provide an excellent tool for the investigation of the impact of environment on the formation and propagation of amyloids.…”

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

“…Other than motor deficits, sleep disturbances, depression, cognitive deficits, and autonomic and sensory dysfunctions are the non-motor associated symptoms of PD (Perez and Palmiter, 2005;Choi et al, 2008;Chesselet et al, 2012). As far as risk factors are concerned, several lines of evidence highlight the involvement of genetic (Lesage and Brice, 2009;Trinh and Farrer, 2013) and environmental (Tanner et al, 2011) factors, and their joint action (Langston et al, 1984a;Schapira, 2006) in the course of PD, where exposure to pesticides has been well recognized as one of the dangerous environmental factors (Langston et al, 1984b;Schmidt and Ferger, 2001;Ascherio et al, 2006;Costello et al, 2009;Matsui et al, 2009;Tanner et al, 2011;Liew et al, 2014;Chen and Ritz, 2018). A plethora of pesticides has been developed and used to increase agriculture productivity (Muthukumaran et al, 2011), and low-dose exposure of humans to pesticides, in general, and herbicides, in particular, is mostly tolerated by healthy humans.…”