散发性帕金森病蛋白酶体功能障碍及其所致的路易(小)体形成
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Dysfunction of Proteasome and Formation of Lewy body in Sporadic Parkinson's Disease
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    摘要:

    散发性帕金森病( sporadic Parkinson's disease,sPD)的主要病理特征之一是中脑黑质致密部(substantia nigra pars compacta,SNpc)残存多巴胺能神经元内核周路易(小)体(Lewy body,LB)形成.LB发生的具体原因和确切过程有待进一步阐释.来自遗传学、尸体解剖和实验科学的报道提示,蛋白酶体功能障碍及其所致的LB形成可能是按照聚集体形成途径 (process of aggresomes)进行的.在聚集体形成途径过程中,异常蛋白质聚集基本上经历了非纤维化分子聚集过程(molecular crowding)以及后续的纤维化聚集过程(fibrilation of aggregation).其间,蛋白酶体功能障碍 (dysfunction of proteasome)、内质网相关降解丧失(loss of endoplasmic reticulum associated degradation)、非纤维化聚集物 (nonfibrilar aggregates) 、聚集体 (aggresomes) 及至纤维化LB (fibrilar LB)等构成了sPD病变过程的主要事件.这提示在sPD病变过程中,蛋白酶体功能障碍及其所致的LB形成过程实质上是细胞信号的转导过程,其间涉及了众多的蛋白质分子.

    Abstract:

    Lewy body (LB) in the substantia nigra pars compacta (SNpc) is one of the cardinal pathological features in sporadic Parkinson's disease (sPD). Both pathogeny and pathomechanism of LB have been set forth. However, genetic, postmortem and experimental evidences demonstrate that impaired proteasomes and concomitant LB could result in the concept of process of aggresomes, by which aggregation reaction of abnormal proteins is mainly proposed as molecular crowding of non-fibrillar proteins followed by fibrillation of aggregated proteins, and in which dysfunction of proteasomes, loss of endoplasmic reticulum-associated degradation (ERAD), aggregates, aggresomes and LB are attractive occurrences in sPD. This suggests that dysfunction of proteasome and concomitant formation of LB in sPD is basically associated with cellular process of signal transduction involved in a variety of proteins.

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李兴安,张应玖,常 明,王丹萍,刘 韬,胡林森.散发性帕金森病蛋白酶体功能障碍及其所致的路易(小)体形成[J].生物化学与生物物理进展,2008,35(5):502-511

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历史
  • 收稿日期:2007-09-14
  • 最后修改日期:2007-11-22
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  • 在线发布日期: 2008-02-03
  • 出版日期: 2008-05-20