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Sulfhydration mediates neuroprotective actions of parkin.

ABSTRACT: Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic Parkinson's disease. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and are investigated by site-directed mutagenesis. Parkin sulfhydration is markedly depleted in the brains of patients with Parkinson's disease, suggesting that this loss may be pathologic. This implies that hydrogen sulfide donors may be therapeutic.

SUBMITTER: Vandiver MS

PROVIDER: S-EPMC3622945 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Sulfhydration mediates neuroprotective actions of parkin.

Vandiver M Scott MS Paul Bindu D BD Xu Risheng R Karuppagounder Senthilkumar S Rao Feng F Snowman Adele M AM Ko Han Seok HS Lee Yun Il YI Dawson Valina L VL Dawson Ted M TM Sen Nilkantha N Snyder Solomon H SH

Nature communications 20130101

Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic Parkinson's disease. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and are investigated by site-directed mu ...[more]

PMID: 23535647

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