Targeting α-synuclein aggregation and its role in mitochondrial dysfunction in Parkinson's disease.

Lewy bodies that contain aggregated α-synuclein (α-syn) in the dopaminergic (DA) neuron are the main culprit behind neurodegeneration in Parkinson's disease (PD). Besides, mitochondrial dysfunction has a well established and prominent role in the pathogenesis of PD. However, the exact mechanism by which α-syn causes dopaminergic neuronal loss was unclear. Recent evidence suggests that aggregated α-syn localises in the mitochondria and contributes to oxidative stress-mediated apoptosis in neurons. Therefore, the involvement of aggregated α-syn in mitochondrial dysfunction-mediated neuronal loss has made it an emerging drug target for the treatment of PD. However, the exact mechanism by which α-syn permeabilises through the mitochondrial membrane and affects the electron transport chain remains under investigation. In the present study, we describe mitochondria-α-syn interactions and how α-syn aggregation modulates mitochondrial homeostasis in PD pathogenesis. We also discuss recent therapeutic interventions targeting α-syn aggregation that may help researchers to design novel therapeutic treatments for PD.