Autophagy: From Molecular Mechanisms to Disease Regulation and Therapeutic Strategies

TL;DR

This review explores how autophagy, a cellular process, influences disease and how it can be targeted for therapies, especially in neurodegenerative and metabolic disorders.

Contribution

The paper integrates recent findings on autophagy regulation, its role in disease, and microbiota interactions, offering new conceptual frameworks for therapeutic strategies.

Findings

Autophagy acts as a bidirectional modulator in neurodegenerative and metabolic diseases, with both protective and harmful effects.

Microbial signals via the gut-brain axis influence autophagy responses and disease progression.

Nanomedicine-based delivery systems are emerging as promising tools for autophagy-targeted therapies.

Abstract

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.

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