Ted M Dawson1, Valina L Dawson. 1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Abstract
BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurologic disorder, which affects approximately one million men and women in the US alone. PD represents a heterogeneous disorder with common clinical manifestations and, for the most part, common neuropathological findings. OBJECTIVE: This short article reviews the role of the ubiquitin E3 ligase in sporadic PD. METHODS: The role of parkin in sporadic PD was reviewed by querying PubMed. RESULTS: Parkin is inactivated in sporadic PD via S-nitrosylation, oxidative and dopaminergic stress, and phosphorylation by the stress-activated kinase c-Abl, leading to the accumulation of AIMP2 and PARIS (ZNF746). CONCLUSION: Strategies aimed at maintaining parkin in a catalytically active state or interfering with the toxicity of AIMP2 and PARIS (ZNF746) offer new therapeutic opportunities.
BACKGROUND:Parkinson's disease (PD) is a chronic progressive neurologic disorder, which affects approximately one million men and women in the US alone. PD represents a heterogeneous disorder with common clinical manifestations and, for the most part, common neuropathological findings. OBJECTIVE: This short article reviews the role of the ubiquitin E3 ligase in sporadic PD. METHODS: The role of parkin in sporadic PD was reviewed by querying PubMed. RESULTS: Parkin is inactivated in sporadic PD via S-nitrosylation, oxidative and dopaminergic stress, and phosphorylation by the stress-activated kinase c-Abl, leading to the accumulation of AIMP2 and PARIS (ZNF746). CONCLUSION: Strategies aimed at maintaining parkin in a catalytically active state or interfering with the toxicity of AIMP2 and PARIS (ZNF746) offer new therapeutic opportunities.
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