NeuroMyoGene Institute-PGNM, CNRS UMR 5261-INSERM U1315, University of Claude Bernard Lyon 1, 69008 Lyon, France.
CHU Montpellier, University of Montpellier, 34295 Montpellier, France.
Cells. 2024 Jan 4;13(1):103. doi: 10.3390/cells13010103.
Autophagy is a major degradative pathway that plays a key role in sustaining cell homeostasis, integrity, and physiological functions. Macroautophagy, which ensures the clearance of cytoplasmic components engulfed in a double-membrane autophagosome that fuses with lysosomes, is orchestrated by a complex cascade of events. Autophagy has a particularly strong impact on the nervous system, and mutations in core components cause numerous neurological diseases. We first review the regulation of autophagy, from autophagosome biogenesis to lysosomal degradation and associated neurodevelopmental/neurodegenerative disorders. We then describe how this process is specifically regulated in the axon and in the somatodendritic compartment and how it is altered in diseases. In particular, we present the neuronal specificities of autophagy, with the spatial control of autophagosome biogenesis, the close relationship of maturation with axonal transport, and the regulation by synaptic activity. Finally, we discuss the physiological functions of autophagy in the nervous system, during development and in adulthood.
自噬是一种主要的降解途径，在维持细胞内环境平衡、完整性和生理功能方面发挥着关键作用。巨自噬通过一个复杂的级联事件来协调，该过程确保了被双层自噬体吞噬的细胞质成分的清除，自噬体与溶酶体融合。自噬对神经系统有特别大的影响，核心成分的突变会导致许多神经疾病。我们首先回顾自噬的调节，从自噬体的生物发生到溶酶体的降解以及相关的神经发育/神经退行性疾病。然后，我们描述了这个过程是如何在轴突和树突-胞体区室中被特异性调节的，以及它在疾病中是如何改变的。特别是，我们介绍了自噬的神经元特异性，包括自噬体生物发生的空间控制、与轴突运输的密切关系以及突触活动的调节。最后，我们讨论了自噬在神经系统中的生理功能，包括在发育和成年期的功能。
