Cross-talk between mitochondria and proteasome in Parkinson's disease pathogenesis
Cross-talk between mitochondria and proteasome in Parkinson's disease pathogenesis
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DOI：
10.3389/fnagi.2010.00017
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发表时间：
2010-05-21
影响因子：
4.8
通讯作者：
Oliveira, Catarina Resende
中科院分区：
文献类型：
--
作者：
Branco, Diogo Martins;Arduino, Daniela M.;Oliveira, Catarina Resende
帕金森病（PD）是最常见的进行性神经退行性运动障碍，其特征在于黑质纹状体多巴胺能神经元的选择性丧失和细胞内不溶性蛋白质内含物（称为Lewy小体）的存在。虽然PD发病机制仍然难以捉摸，但特定神经元死亡的主要假设确定线粒体功能障碍，泛素-蛋白酶体系统（UPS）的改变和氧化应激是协同作用导致这种毁灭性疾病的主要事件。在这篇综述中，我们将重点关注线粒体损伤及其对蛋白酶体功能和α-突触核蛋白聚集的影响。我们将讨论线粒体和蛋白酶体串扰在导致PD的神经元丢失中的作用，并讨论这些知识如何进一步改善患者治疗。
Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder, characterized by the selective loss of nigrostriatal dopaminergic neurons, and the presence of intracellular insoluble proteinaceous inclusions, known as Lewy Bodies. Although PD etiopathogenesis remains elusive, the leading hypothesis for the death of specific groups of neurons establishes that mitochondrial dysfunction, alterations in the ubiquitin-proteasomal system (UPS), and oxidative stress are major events that act synergistically causing this devastating disease. In this review we will focus on mitochondrial impairment and its implications on proteasomal function and alpha-synuclein aggregation. We will address the role of mitochondria and proteasome cross-talk in the neuronal loss that leads to PD and discuss how this knowledge might further improve patient therapy.