Cell Death Mechanisms of Neurodegeneration
Cell Death Mechanisms of Neurodegeneration
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DOI：
10.1007/978-3-319-57193-5_16
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Dawson, Valina L.
中科院分区：
文献类型：
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作者：
Fan, Jing;Dawson, Ted M.;Dawson, Valina L.
遗传或病理学上不同的神经退行性疾病有共同的机制，如兴奋性毒性、线粒体缺陷和氧化应激、蛋白质错误折叠和翻译功能障碍、自噬和小胶质细胞活化。这表明，虽然原始原因可能在个别疾病甚至某些疾病的亚型中有所不同，但这些破坏的共同细胞功能和信号传导，以及衰老，可能导致通过类似途径最终执行细胞死亡。各种神经退行性疾病症状可能是由遭受功能障碍和损失的细胞群的类型、位置和连接引起的。除了细胞凋亡、坏死性凋亡和自噬之外，一种重要的死亡形式，称为死亡原（parthanatos），在中风和几种神经退行性疾病中起着突出的作用，这是由于PARP-1过度活化、PAR积累、线粒体蛋白AIF的核转位和大规模DNA切割。了解细胞死亡信号的机制和相互作用不仅有助于开发神经保护策略来阻止神经退行性变，还可以提供监测疾病进展和恢复的生物标志物。
There are common mechanisms shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. This indicates that although the original cause may differ in individual diseases or even subtypes of certain disorders, these disrupted common cell functions and signaling, together with aging, may lead to final execution of cell death through similar pathways. The variable neurodegenerative disease symptoms are probably caused by the type, location, and connection of the cell populations that suffer from dysfunction and loss. Besides apoptosis, necroptosis, and autophagy, an important form of death termed parthanatos plays a prominent role in stroke and several neurodegenerative diseases, which is due to PARP-1 over-activation, PAR accumulation, nuclear translocation of the mitochondria protein AIF, and large-scale DNA cleavage. Understanding the mechanisms and interactions of cell death signaling will not only help to develop neuroprotective strategies to halt neurodegeneration, but also provide biomarkers for monitoring disease progression and recovery.