PMC:3023298 / 93408-94680
Annnotations
2_test
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is a soluble monomeric protein that can associate with mitochondrial membranes [342]. α-Syn can be induced to polymerize into insoluble fibrils due to a conformational change from an α-helical coil to a β-pleated sheet [343]. α-Syn is a major structural component of LBs (Figure 4F), forming the ~10-nm fibrils, but in most neurodegenerative diseases, LBs are associated with accumulation of wild-type, not mutant, α-Syn [319]. α-Syn mutations cause increased levels of protofibrils, possibly being the more toxic form of the protein [344]. α-Syn protofibrils might also be toxic by making membranes of cells more porous [345]. Over-expression of human wild-type or mutant α-Syn in cultured cells elevates the generation of intracellular ROS [346,347] and causes mitochondrial deficits [346]; moreover, expression of mutant α-Syn increases cytotoxicity to dopamine oxidation products [348]. Aggregation of wild-type and mutated α-Syn is associated with enhanced cell death in cultured cells [349]. Nitration of α-Syn, signifying the presence of potent reactive nitrogen species such as ONOO- or its free radical derivative nitrogen dioxide (NO2), is a major signature of human PD and other synuclinopathies and might be critical to the aggregation process [350,351]."}