Autophagy is an evolutionarily conserved pathway for delivering cytoplasmic cargo to lysosomes for degradation. In its classically studied form, autophagy is a stress response induced by starvation to recycle building blocks for essential cellular processes. In addition, autophagy maintains basal cellular homeostasis by degrading endogenous substrates such as cytoplasmic proteins, protein aggregates, damaged organelles, as well as exogenous substrates such as bacteria and viruses. Given their important role in homeostasis, autophagy and lysosomal machinery are genetically linked to multiple human disorders such as chronic inflammatory diseases, cardiomyopathies, cancer, and neurodegenerative diseases. Multiple targets within the autophagy and lysosomal pathways offer therapeutic opportunities to benefit patients with these disorders. Here, I will summarize the mechanisms of autophagy pathways, the evidence supporting a pathogenic role for disturbed autophagy and lysosomal degradation in nervous system disorders, and the therapeutic potential of autophagy modulators in the clinic.

自噬是一种进化上保守的途径，用于将细胞质货物递送至溶酶体进行降解。在其经典研究的形式中，自噬是一种由饥饿引起的应激反应，可循环用于基本细胞过程的构建基块。另外，自噬通过降解内源性底物如细胞质蛋白，蛋白质聚集体，受损的细胞器以及外源性底物如细菌和病毒来维持基础细胞的稳态。由于自噬和溶酶体机制在稳态中具有重要作用，因此与多种人类疾病（如慢性炎症性疾病，心肌病，癌症和神经退行性疾病）遗传相关。自噬和溶酶体途径中的多个靶标为使这些疾病的患者受益提供了治疗机会。这里，