Autophagy: From Molecular Mechanisms to Disease Regulation and Therapeutic Strategies

Autophagy is increasingly recognized as a context-dependent regulatory process that links cellular quality control with systemic metabolic and neurological homeostasis. However, how distinct autophagy pathways contribute to disease progression, and how they are dynamically modulated by host-microbiota interactions, remain incompletely understood. In this review, we synthesize recent advances in the molecular regulation of macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), with a particular emphasis on selective autophagy and its disease-specific functions. We examine emerging evidence implicating autophagy as a bidirectional modulator in neurodegenerative and metabolic disorders, highlighting conditions under which autophagy exerts protective versus maladaptive effects. Importantly, we integrate recent findings on the microbiota-gut-brain axis to illustrate how microbial signals reshape autophagic responses and influence disease susceptibility and progression. Finally, we summarize current progress and limitations in autophagy-targeted therapeutic strategies, including nanomedicine-based delivery systems, and propose conceptual frameworks to guide the development of precise, context-aware autophagy interventions. This review provides an updated and integrative perspective that bridges molecular mechanisms, host-microbiota crosstalk, and translational opportunities in autophagy-related diseases.