Fig. 1

General autophagy process and targets for potential drugs inducing autophagy. Autophagy can be induced by stress, energy deficiency, increased intracellular Ca²⁺, etc., through inhibition of the mTOR complex and subsequent activation of the ULK complex. The class III PI3K complex can be phosphorylated by ULK, subsequently catalyzing PI into PI3P and initiating autophagy. Atg9 vesicles are released from the Golgi complex and recruit the PI3K complex to downstream autophagy-related proteins. The Atg12-Atg5-Atg16L complex and LC3 are ubiquitin ligases that are indispensable for membrane elongation and closure. LC3 can be cleaved by Atg4, and the generated LC3-I binds with PE, which is mediated by the Atg12-Atg5-Atg16L complex, localized on the membranes of autophagosomes. The dynein-dynactin complex mediates the transportation of organelles along the microtubule. Mature vesicles labeled by LC3 are distributed along microtubules and LC3 colocalizes with dynein-dynactin complex. mSOD1 alters the cellular localization of dynein and inhibits the dynein-dynactin complex, impeding the transportation of autophagosomes. TFEB is regulated by mTORC1 to mediate the expression of autophagy and lysosome-related protein (atg9B and LAMP1), which in turn affects the formation of autolysosome. mSOD1 also interferes with the expression of TFEB. Rab7 regulates the formation and maturation of autolysosome, and interacts with C9ORF72. Lithium and n-butylidenephthalide enhance autophagy by inhibiting PI3K and GSK-3β, Rapamycin and Torkinib induce autophagy by inhibiting mTORC1, while carbamazepine, verapamil and trehalose initiate autophagy by activating AMPK. Also, trehalose regulates the phosphorylation and translocation of TFEB. It has been reported that ropinirole induces autophagy through a Beclin-1-dependent pathway. HDAC6 can control the fusion of autophagosomes and lysosomes. mTORC1: mechanistic target of rapamycin complex 1, ULK1: unc-51-like kinase 1, AMPK: AMP-activated protein kinase, PI3K: phosphoinositide 3-kinase, GSK-3β: glycogen synthase kinase-3β, PI: phosphatidylinositol, PI3P: phosphatidylinositol-3-phosphate, Atg: autophagy-related protein, LC3: microtubule-associated protein 1A/1B-light chain 3, PE: phosphatidyl ethanolamine, mSOD1: mutant SOD1, TFEB: transcription factor EB, LAMP1: lysosomal-associated membrane protein 1, Rab7: Ras-related protein 7