Exploring the interplay between metabolomics and genetics in Parkinson's disease: Insights from ongoing research and future avenues

Parkinson's disease (PD) is a widespread neurodegenerative disorder, whose complex aetiology remains under construction. While rare variants have been associated with the monogenic PD form, most PD cases are influenced by multiple genetic and environmental aspects. Nonetheless, the pathophysiological pathways and molecular networks involved in monogenic/idiopathic PD overlap, and genetic variants are decisive in elucidating the convergent underlying mechanisms of PD. In this scenario, metabolomics has furnished a dynamic and systematic picture of the synergy between the genetic background and environmental influences that impact PD, making it a valuable tool for investigating PD-related metabolic dysfunctions. In this review, we performed a brief overview of metabolomics current research in PD, focusing on significant metabolic alterations observed in idiopathic PD from different biofluids and strata and exploring how they relate to genetic factors associated with monogenic PD. Dysregulated amino acid metabolism, lipid metabolism, and oxidative stress are the critical metabolic pathways implicated in both genetic and idiopathic PD. By merging metabolomics and genetics data, it is possible to distinguish metabolic signatures of specific genetic backgrounds and to pinpoint subgroups of PD patients who could derive personalized therapeutic benefits. This approach holds great promise for advancing PD research and developing innovative, cost-effective treatments.