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

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