Mitochondrial-Derived Vesicles as Candidate Biomarkers in Parkinson's Disease: Rationale, Design and Methods of the EXosomes in PArkiNson Disease (EXPAND) Study

Abstract

The progressive loss of dopaminergic neurons in the nigro-striatal system is a major trait of Parkinson's disease (PD), manifesting clinically as motor and non-motor symptoms. Mitochondrial dysfunction and oxidative stress are alleged pathogenic mechanisms underlying aggregation of misfolded α-synuclein that in turn triggers dopaminergic neurotoxicity. Peripheral processes, including inflammation, may precede and contribute to neurodegeneration. Whether mitochondrial dyshomeostasis in the central nervous system and systemic inflammation are linked to one another in PD is presently unclear. Extracellular vesicles (EVs) are delivery systems through which cells can communicate or unload noxious materials. EV trafficking also participates in mitochondrial quality control (MQC) by generating mitochondrial-derived vesicles to dispose damaged organelles. Disruption of MQC coupled with abnormal EV secretion may play a role in the pathogenesis of PD. Furthermore, due to its bacterial ancestry, circulating mitochondrial DNA can elicit an inflammatory response. Therefore, purification and characterisation of molecules packaged in, and secreted through, small EVs (sEVs)/exosomes in body fluids may provide meaningful insights into the association between mitochondrial dysfunction and systemic inflammation in PD. The EXosomes in PArkiNson Disease (EXPAND) study was designed to characterise the cargo of sEVs/exosomes isolated from the serum of PD patients and to identify candidate biomarkers for PD.