Mitochondrial Dysfunction in Parkinson's Disease: Pathogenesis and Neuroprotection

Figure 1

Genetic mutation of α-synuclein and subsequent protein and biochemical alterations. Modifications to the α-synuclein gene cause dysfunction of its protein product. Proteasomal activity becomes impaired, leading to an increased tendency for the protein to aggregate. Mutated α-synuclein protein also localises at the inner mitochondrial membrane, causing complex I dysfunction. ATP production is subsequently reduced, as is the transmembrane potential of the organelle. Increased levels of ROS result, and with mtDNA being particularly susceptible to ROS damage, further cell stress occurs. The acidic cytosolic environment created by ROS and metabolic impairment results in the activation of cell death mediators, such as cytochrome c. Apoptotic pathways are initiated and cell death subsequently occurs.