Molecular profiling in Parkinson's: current approaches, progress and challenges

Description

Parkinson’s disease (PD) is a progressive neurodegenerative disease that manifests with a wide range of disease phenotypes and rates of progression. Treatments that can prevent, delay, or halt disease progression in PD are non-existing. One of the key barriers to the development of effective treatment paradigms for PD is the lack of detailed knowledge of the initial molecular pathways involved in physiological and early pathological conditions and lack of diagnostic and prognostic biomarkers. Recent intriguing findings from my team and others suggest that disturbed cellular (vesicular) trafficking, lipid metabolism, and dysfunctional organelles are among the initial cellular pathologies associated with/leading to alpha-synuclein (aSyn) aggregation and generalized cellular dysfunction in PD. In this context, we posit that studying these initial mechanisms leading to aSyn aggregation in brain and biofluids of well-characterized and genotyped PD patients may aid in defining molecular subtypes in PD. Here, we review current approaches, progress and challenges in defining molecular profiles in PD with a focus on the following topics: 1) pathogenic mechanisms leading to aSyn aggregation (upstream); 2) molecular aSyn profiles and strains; 3) neurotoxic consequences of aSyn aggregation (downstream). Rigorous correlative analysis of aSyn molecular profiles and up- and downstream mechanisms of aSyn aggregation in patient biomaterial may aid in defining molecular subtypes in PD. Ongoing efforts on studying molecular profiles in biomaterial in large multicenter longitudinal patient cohorts with multimodal approaches hold promise in the search for diagnostic and prognostic biomarkers reflecting pathogenic mechanisms driving disease progression in PD.

Period	10 Jun 2021
Event title	Dutch Neuroscience meeting: neuro-immunology in neurological diseases
Event type	Conference
Degree of Recognition	National