Autophagic activity in neuronal cell death

• Published in: Neuroscience bulletin 2015-08, Vol.31 (4), p.382-394
• Main Authors: Button, Robert W., Luo, Shouqing, Rubinsztein, David C.
• Format: Article
• Language: English
• Subjects: Anatomy; Anesthesiology; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Brain - physiology; Cell Survival; Human Physiology; Humans; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - physiopathology; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurology; Neurons - metabolism; Neurons - physiology; Neurosciences; Pain Medicine; Review; 有丝分裂; 神经元细胞; 神经细胞死亡; 神经退行性疾病; 程序性细胞死亡; 能量需求; 自噬; 高活性
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-015-1528-y

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.