Genetic and environmental risk factors of Parkinsonism

Apr 6, 2026Journal of neural transmission (Vienna, Austria : 1996)

Genetic and environmental factors linked to Parkinsonism

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Abstract

Genetic variants may explain a significant fraction of the etiology of sporadic parkinsonian disorders.

Parkinsonian disorders include a variety of neurodegenerative diseases linked to different pathogenic processes.
Pathological proteins lead to brain diseases known as synucleinopathies, tauopathies, or TDP-43 proteinopathies.
Genetic risk factors are related to processes that disturb cellular function, such as protein aggregation and membrane trafficking.
Environmental risk factors, particularly pesticides and trichlorethylene, are associated with the development of neurodegenerative proteinopathy.
Three types of endemic Parkinsonism—Western Pacific Parkinsonism, Caribbean Parkinsonism, and a cluster in North France—are thought to have environmental causes.

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Parkinsonian disorders comprise a broad spectrum of neurodegenerative diseases with a wide variety of pathogenetic processes. These processes lead to the formation of pathological proteins, resulting in the brain diseases called synucleinopathies, tauopathies or TDP-43 proteinopathies. There is currently growing support for the hypothesis that genetic variants explain a significant fraction of the etiology of apparently sporadic parkinsonian disorders. Genetic risk factors can be stratified according to the metabolic or structural processes that can lead to cellular disturbance; these processes involve protein aggregation, protein and membrane trafficking, stabilization of the neurite structure, prion-like transmission of pathological proteins, ubiquitin-proteasome system balance, mitophagy, lysosome autophagy, synaptic functions, and dopamine transmission. Regarding the environmental risk factors, there are several substances that have been supposed of being a risk for the development of neurodegenerative proteinopathy and Parkinsonism, mainly the agents used in agriculture and the textile industry. The most important and most frequently studied are pesticides and trichlorethylene. Beside the globally ubiquitous substances which are supposedly neurotoxic and exposure to which can cause manifestations of Parkinsonism, there are more geographically (regionally) specific substances, which cause (or quite recently caused) the manifestation of endemically present Parkinsonism. Among ten types of endemic Parkinsonism, three of them are thought to have an environmental cause: Western Pacific Parkinsonism, Caribbean Parkinsonism, and North France cluster of atypical Parkinsonism.

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Genetic and environmental risk factors of Parkinsonism

Abstract

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