What causes the build-up of ubiquitin-containing inclusions in Parkinson's disease?
What causes the build-up of ubiquitin-containing inclusions in Parkinson's disease?
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DOI：
10.1016/s0047-6374(00)00150-0
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发表时间：
2000-09-01
影响因子：
5.3
通讯作者：
Andersen, JK
中科院分区：
文献类型：
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作者：
Andersen, JK
帕金森病 (PD) 的特征是中脑中存在称为路易体的神经元包涵体。这些蛋白质细胞内沉积物可能导致该大脑区域随后的多巴胺能神经变性。虽然许多研究人员认为帕金森病相关路易体中的免疫阳性泛素染色代表细胞内泛素-蛋白质缀合物水平升高，但这尚未得到明确证明。 PD 中脑中氧化应激的增加以及硫醇调节分子谷胱甘肽水平的降低可能会导致泛素化系统的重要成分发生 S-硫醇化，从而大大降低其活性，实际上损害细胞泛素化蛋白质的能力。在这里，我们回顾了帕金森病相关路易体中游离泛素与蛋白质结合泛素的证据，并讨论了解决这一重要问题的未来方向及其对未来治疗的影响。 (C) 2000 Elsevier Science Ireland Ltd. 保留所有权利。
Parkinson's disease (PD) is characterized by the presence of neuronal inclusions in the midbrain known as Lewy bodies. These proteinaceous intracellular deposits may contribute to subsequent dopaminergic neurodegeneration in this brain region. While it is assumed by many investigators that immunopositive ubiquitin staining in Parkinson's-associated Lewy bodies represents the presence of elevated levels of intracellular ubiquitin-protein conjugates, this has yet to be definitively proven. Increases in oxidative stress along with decreased levels of the thiol regulatory molecule glutathione in the midbrain in PD may cause S-thiolation of important components of the ubiquitination system drastically reducing their activities and in fact impairing the cell's ability to ubiquitinate proteins at all. Here, we review evidence for free versus protein-bound ubiquitin in Parkinsonian-associated Lewy bodies and discuss future directions towards resolving this important question as well as its implication for future treatment therapies. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.