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Fig. 2 | Molecular Neurodegeneration

Fig. 2

From: PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease

Fig. 2

Mechanisms of Parkin inactivation in sporadic PD. To date, the two most widely studied mechanisms by which Parkin is inactivated in sporadic PD is through chemical modifications leading to impaired enzyme activity (dopamine adducts, S-nitrosylation), and through α-synuclein aggregation. α-Synuclein aggregates lead to the activation of stress-induced kinases c-Abl and p38 MAPK, which phosphorylate and inactivate Parkin. These mechanisms therefore suggest that studies on the molecular mechanisms of neurodegeneration caused by complete Parkin loss (ie. Genetic knockout) may also be common mechanism of neurodegeneration between Parkin-induced PD and sporadic PD of unclear etiology. Some of these downstream pathways of neurodegeneration include (neuro)-immune overactivation, mitochondrial deficits, and the accumulation of Parkin substrates leading to activation of cell-death pathways

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