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

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.