Autophagy and endolysosomal trafficking are crucial in neuronal development, function and survival. These processes ensure efficient removal of misfolded aggregation-prone proteins and damaged organelles, such as dysfunctional mitochondria, thus allowing the maintenance of proper cellular homeostasis. Beside this, emerging evidence has pointed to their involvement in the regulation of the synaptic proteome needed to guarantee an efficient neurotransmitter release and synaptic plasticity. Along this line, an intimate interplay between the molecular machinery regulating synaptic vesicle endocytosis and synaptic autophagy is emerging, suggesting that synaptic quality control mechanisms need to be tightly coupled to neurosecretion to secure release accuracy. Defects in autophagy and endolysosomal pathway have been associated with neuronal dysfunction and extensively reported in Alzheimer’s, Parkinson’s, Huntington’s and amyotrophic lateral sclerosis among other neurodegenerative diseases, with common features and emerging genetic bases. In this review, we focus on the multiple roles of autophagy and endolysosomal system in neuronal homeostasis and highlight how their defects probably contribute to synaptic default and neurodegeneration in the above-mentioned diseases, discussing the most recent options explored for therapeutic interventions.

自噬和溶酶体运输对神经元发育，功能和存活至关重要。这些过程可确保有效清除易折叠的聚集蛋白和受损的细胞器（例如功能异常的线粒体），从而维持适当的细胞体内平衡。除此之外，越来越多的证据表明它们参与调节突触蛋白质组，以保证有效的神经递质释放和突触可塑性。沿着这条线，调节突触小泡内吞作用和突触自噬的分子机制之间的密切相互作用正在出现，这表明突触质量控制机制需要紧密结合神经分泌以确保释放的准确性。自噬和溶酶体途径的缺陷与神经元功能障碍有关，在阿尔茨海默氏病，帕金森氏病，亨廷顿氏病和肌萎缩性侧索硬化症以及其他神经退行性疾病中得到了广泛报道，具有共同特征和新出现的遗传基础。在这篇综述中，我们关注自噬和溶酶体系统在神经元稳态中的多种作用，并强调它们的缺陷可能如何导致上述疾病的突触默认和神经退行性变，并探讨了治疗性干预措施的最新选择。