Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA; email:
Annu Rev Cell Dev Biol. 2019 Oct 6;35:477-500. doi: 10.1146/annurev-cellbio-100818-125242. Epub 2019 Jul 23.
Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. Autophagy is particularly important in neurons, which are terminally differentiated cells that must last the lifetime of the organism. There are both constitutive and stress-induced pathways for autophagy in neurons, which catalyze the turnover of aged or damaged mitochondria, endoplasmic reticulum, other cellular organelles, and aggregated proteins. These pathways are required in neurodevelopment as well as in the maintenance of neuronal homeostasis. Here we review the core components of the pathway for autophagosome biogenesis, as well as the cell biology of bulk and selective autophagy in neurons. Finally, we discuss the role of autophagy in neuronal development, homeostasis, and aging and the links between deficits in autophagy and neurodegeneration.
自噬是降解功能失调的细胞器和蛋白聚集体的主要细胞途径。自噬在神经元中尤为重要，神经元是终末分化的细胞，必须维持生物体的寿命。神经元中既有组成型的自噬途径，也有应激诱导的自噬途径，它们可以催化衰老或受损的线粒体、内质网、其他细胞细胞器和聚集蛋白的周转。这些途径在神经发育以及神经元内环境稳定的维持中是必需的。在这里，我们综述了自噬体生物发生途径的核心成分，以及神经元中巨自噬和选择性自噬的细胞生物学。最后，我们讨论了自噬在神经元发育、内环境稳定和衰老中的作用，以及自噬缺陷与神经退行性变之间的联系。
