Proteasomal function is impaired in substantia nigra in Parkinson's disease
Proteasomal function is impaired in substantia nigra in Parkinson's disease
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DOI：
10.1016/s0304-3940(00)01701-8
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发表时间：
2001-01-19
影响因子：
2.5
通讯作者：
Jenner, P
中科院分区：
文献类型：
--
作者：
McNaught, KSP;Jenner, P
特发性帕金森病 (PD) 黑质退化多巴胺能神经元中 α-突触核蛋白、泛素和其他蛋白质在路易体中的积累表明，抑制正常/异常蛋白质降解可能导致神经元死亡。我们现在首次表明，PD 黑质中 20/26S 蛋白酶体的胰凝乳蛋白酶（39%）、胰蛋白酶（42%）和后酸样（33%）水解活性受损。蛋白酶体抑制似乎不是由药物治疗引起的，因为高浓度的 L-3,4-二羟基苯丙氨酸对体外酶活性没有影响。这些观察结果提供了第一个直接证据，表明抑制泛素-蛋白酶体途径导致蛋白质处理和路易体形成改变可能是特发性帕金森病黑质纹状体途径退化的原因。 (C) 2001 年，爱思唯尔科学爱尔兰有限公司出版。
The accumulation of alpha -synuclein, ubiquitin and other proteins in Lewy bodies in degenerating dopaminergic neurones in substantia nigra in idiopathic Parkinson's disease (PD) suggest that inhibition of normal/abnormal protein degradation may contribute to neuronal death. We now show for the first time that the chymotrypsin- (39%), trypsin- (42%) and postacidic-like (33%) hydrolysing activities of 20/26S proteasome are impaired in substantia nigra in PD. Proteasome inhibition does not appear to result from drug treatment since high concentrations of L-3,4-dihydroxyphenylalanine had no effect on enzymatic activity in vitro. These observations provide the first direct evidence that inhibition of the ubiquitin-proteasome pathway leading to altered protein handling and Lewy body formation may be responsible for degeneration of the nigrostriatal pathway in idiopathic PD. (C) 2001 Published by Elsevier Science Ireland Ltd.