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 α-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.

Keywords: Parkinson’s disease; environmental risk factors; etiology; prodromal symptoms; progression.

Fig.1

Systematic and Life-long Approach to Study Environmental Triggers and Modifiers for PD Development. Late-onset sporadic PD takes decades to develop. In early- to mid-life, some environmental toxicants (e.g., pesticides, air pollutants, virus) may enter the body via the nose or the mouth, which may induce pathological synucleinopathy in susceptible individuals via mechanisms such as inflammation or microbiome dysbiosis; over time, the pathology may progress to the central olfactory structures and/or the lower brain stem and induce symptoms such as olfactory impairment and sleep disturbances. A portion of affected individuals may further develop motor deficits over years, which may eventually lead to a PD diagnosis. During this prolonged process, many environmental factors may come into play at various time windows to perpetuate or slow down the disease prodromal progression. Modified from Chen H (2018). J Parkinsons Dis. 8, 1–12.