Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps.
Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps.
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DOI：
10.1007/s10495-008-0309-3
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发表时间：
2009-04
期刊：
影响因子：
7.2
通讯作者：
Greene, Lloyd A.
中科院分区：
文献类型：
--
作者：
Levy, Oren A.;Malagelada, Cristina;Greene, Lloyd A.
帕金森病（PD）是一种常见的神经退行性疾病。PD中的神经元细胞死亡仍然知之甚少，尽管有丰富的潜在致病机制和途径。几种细胞系统的缺陷被认为是导致细胞走向神经元死亡的早期触发因素。这些包括异常蛋白质积累，特别是α-突触核蛋白;通过多种途径改变蛋白质降解;线粒体功能障碍;氧化应激;神经炎症;和激酶信号转导失调。随着这些系统功能障碍的增加，与细胞死亡更明确相关的途径被招募。这些包括JNK信号传导、p53活化、细胞周期再活化和通过bcl-2家族蛋白的信号传导。最终，神经元变得不堪重负和退化;然而，甚至PD中最终细胞死亡的机制仍然不确定。在这篇综述中，我们将讨论与PD相关的细胞死亡触发因子和效应因子，突出重要的未解决的问题和神经保护疗法的发展的影响。
Parkinson’s disease (PD) is a common neurodegenerative disease. Neuronal cell death in PD is still poorly understood, despite a wealth of potential pathogenic mechanisms and pathways. Defects in several cellular systems have been implicated as early triggers that start cells down the road towards neuronal death. These include abnormal protein accumulation, particularly of alpha-synuclein; altered protein degradation via multiple pathways; mitochondrial dysfunction; oxidative stress; neuroinflammation; and dysregulated kinase signaling. As dysfunction in these systems mounts, pathways that are more explicitly involved in cell death become recruited. These include JNK signaling, p53 activation, cell cycle re-activation, and signaling through bcl-2 family proteins. Eventually, neurons become overwhelmed and degenerate; however, even the mechanism of final cell death in PD is still unsettled. In this review, we will discuss cell death triggers and effectors that are relevant to PD, highlighting important unresolved issues and implications for the development of neuroprotective therapies.
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影响因子：
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