Sulfhydration mediates neuroprotective actions of parkin.

Sulfhydration mediates neuroprotective actions of parkin.
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DOI:
10.1038/ncomms2623
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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帕金森氏病(PD)患者脑内S亚硝化增加和神经保护性泛素E3连接酶PARKIN失活被认为是帕金森病(PD)的致病因素,提示PARKIN可能与散发性PD有关。在这里,我们证明了用硫化氢(H_2S)对Parkin进行生理修饰,称为硫水化,提高了它的催化活性。通过质谱分析鉴定硫水化位点,并通过定点突变进行研究。帕金硫水合作用在帕金森氏病患者的脑中明显耗尽,这表明这种丧失可能是病理性的。这意味着硫化氢捐赠者可能具有治疗作用。
Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson’s Disease (PD) are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic PD. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide (H2S), termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and investigated by site directed mutagenesis. Parkin sulfhydration is markedly depleted in the brains of patients with PD, suggesting that this loss may be pathologic. This implies that H2S donors may be therapeutic.
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