A multi-dimensional view on the etiology of Parkinson’s disease

TL;DR

Parkinson’s disease is likely caused by a complex mix of genetic, environmental, and metabolic factors, suggesting a need for personalized treatment approaches.

Contribution

The paper proposes a multi-dimensional model for Parkinson’s disease etiology, integrating genetic, environmental, epigenetic, and metabolic factors.

Findings

Cytochromes P450 are suggested as a model for how metabolic pathways contribute to Parkinson’s disease.

Parkinson’s disease may result from a combination of genetic variants and environmental factors like pesticides.

Personalized therapy could emerge from understanding individual contributions of these multi-dimensional factors.

Abstract

Parkinson’s disease (PD) has been proposed to be a predominantly genetic versus a mainly environmental disease. We suggest to consider PD rather as a disease caused by multi-dimensional factors, including genetic and environmental, but also epigenetic and metabolic effects. This view is supported by very recently published data on the role of cytochromes P450 (P450s) as a model for a participation of different metabolic pathways to PD. P450s are involved in a broad variety of physiological reactions in the human body and, in addition, play a fundamental role in the detoxification of environmental compounds. Therefore, the majority of PD cases is likely based on a complex interplay between disturbances in genes and the corresponding proteins, which catalyze various metabolic pathways, as well as epigenetic, physiological and environmental effects contributing to PD symptoms. In this context, PD can be caused by one gene mutation (in rare cases), by a combination of variants in different genes, and by an association of environmental factors (e.g. pesticides) with such variants. Characterization of these factors in each individual patient opens up new avenues for a personalized therapy.

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