Axonal autophagy: Mini-review for autophagy in the CNS

NEUROSCIENCE LETTERS

卷:697

Review

Stavoe, Andrea K. H.¹  Holzbaur, Erika L. F.¹ 

[1] Univ Penn, Perelman Sch Med, Dept Physiol, 638A Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA

关键词: Macroautophagy;    Autophagosome biogenesis;    Neuronal homeostasis;    Axon degeneration;    Mitophagy;   

DOI  :  10.1016/j.neulet.2018.03.025

来源: Elsevier

【 摘 要 】

Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the distal axon occurs via a conserved pathway that is required to maintain functional synapses and prevent axon degeneration. Autophagosomes are formed de novo at the axon terminal in a stepwise assembly process, engulfing mitochondrial fragments, aggregated proteins, and bulk cytosol in what appears to be a nonselective uptake mechanism. Following formation, autophagosomes fuse with late endosomes/lysosomes and then are rapidly and efficiently transported along the axon toward the soma, driven by the microtubule motor cytoplasmic dynein. Motile autophagosomes mature to autolysosomes in transit by fusing with additional late endosomes/lysosomes, arriving at the soma as fully competent degradative organelles. Misregulation of neuronal autophagy leads to axonal degeneration and synaptic destabilization, and has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and ALS.

【 授权许可】

Free