Autophagy promotion

Autophagy promotion refers to the therapeutic stimulation of macroautophagy, a conserved lysosomal degradation pathway essential for maintaining cellular homeostasis by removing misfolded proteins and damaged organelles [1, 3]. This process is regulated by a complex network of signaling molecules, primarily the mTOR and AMPK pathways, which control the initiation and maturation of double-membrane vesicles called autophagosomes [4, 8]. In neurodegenerative diseases, promoting autophagy helps clear toxic protein aggregates like amyloid-beta or alpha-synuclein [3, 6]. However, the role of autophagy is context-dependent; while it can act as a tumor suppressor in early cancer stages, it may also support the survival of established tumor cells under stress [1, 5]. Pharmacological agents such as mTOR inhibitors (e.g., rapamycin) and AMPK activators (e.g., metformin) are commonly used to induce this pathway for various clinical applications [5, 7].

Other names

Autophagy inductionAutophagy activationMacroautophagy stimulationPro-autophagic signaling

Autophagy promotion is typically achieved through the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) or the activation of AMP-activated protein kinase (AMPK) [1, 8]. These pathways regulate the Unc-51 like autophagy activating kinase 1 (ULK1) complex, which initiates phagophore formation [4, 6]. This is followed by the recruitment of the Class III PI3K complex (including Beclin-1 and VPS34) and the ATG conjugation systems, such as the ATG12-ATG5-ATG16L1 complex, to facilitate autophagosome maturation and subsequent lysosomal fusion [6, 9, 10].