Figure 4

Summary of α-synuclein’s role in Parkinson’s disease pathology. Cellular α-synuclein levels or chemical structure may be altered by overexpression, mutations, or chemical modifications (such as phosphorylation, nitration, oxidation, exposure to metal ions or toxins, or adduct formation with dopamine quinone). The increased oxidative environment of dopaminergic neurons is likely to exacerbate some of these processes, making these cells especially vulnerable. The end result is increased oligomer formation that may damage mitochondrial membranes. The amyloid-containing Lewy body is likely to be much less toxic than this precursor, and it may be the case that cells that rapidly produce Lewy bodies survive best. Other mutations in parkin, PINK1, and DJ-1 are likely to compromise the ability of mitochondria to resist stress.