Button Robert W, Luo Shouqing, Rubinsztein David C
Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth, PL6 8BU, UK.
Neurosci Bull. 2015 Aug;31(4):382-94. doi: 10.1007/s12264-015-1528-y. Epub 2015 Jun 15.
As post-mitotic cells with great energy demands, neurons depend upon the homeostatic and waste-recycling functions provided by autophagy. In addition, autophagy also promotes survival during periods of harsh stress and targets aggregate-prone proteins associated with neurodegeneration for degradation. Despite this, autophagy has also been controversially described as a mechanism of programmed cell death. Instances of autophagic cell death are typically associated with elevated numbers of cytoplasmic autophagosomes, which have been assumed to lead to excessive degradation of cellular components. Due to the high activity and reliance on autophagy in neurons, these cells may be particularly susceptible to autophagic death. In this review, we summarize and assess current evidence in support of autophagic cell death in neurons, as well as how the dysregulation of autophagy commonly seen in neurodegeneration can contribute to neuron loss. From here, we discuss potential treatment strategies relevant to such cell-death pathways.
作为具有巨大能量需求的终末分化细胞，神经元依赖自噬提供的稳态和废物回收功能。此外，自噬还能在严苛应激期间促进细胞存活，并靶向与神经退行性变相关的易聚集蛋白进行降解。尽管如此，自噬也一直存在争议地被描述为一种程序性细胞死亡机制。自噬性细胞死亡的实例通常与细胞质自噬体数量增加有关，人们认为这会导致细胞成分过度降解。由于神经元中自噬的高活性和依赖性，这些细胞可能特别容易发生自噬性死亡。在这篇综述中，我们总结并评估了支持神经元自噬性细胞死亡的当前证据，以及神经退行性变中常见的自噬失调如何导致神经元丢失。在此基础上，我们讨论了与此类细胞死亡途径相关的潜在治疗策略。
