Cytoskeleton-mediated autophagy regulation in neuroimmune contexts: molecular mechanisms and functional perspectives.

Abstract

This review systematically summarizes the central roles and molecular mechanisms of the cytoskeletal system-including actin filaments, microtubules (MT), intermediate filaments, and the Septin family-in the regulation of autophagy. The cytoskeleton not only provides a structural framework and facilitates transport for the autophagic process but also acts as a dynamic signaling hub, participating in every stage from autophagosome formation and cargo recognition to targeted trafficking and autophagosome-lysosome fusion. Actin filaments regulate the initiation of autophagy through dynamic assembly, Arp2/3-mediated nucleation, and mechanosensing. Microtubules drive the transport and localization of autophagosomes by relying on "dynamic instability" and the "tubulin code". Intermediate filaments-such as vimentin-and septins influence autophagy flux by maintaining organelle integrity, forming molecular scaffolds, and establishing diffusion barriers on membranes. This review further discusses the functional implications of this regulatory network in diverse physiological and pathological neuroimmune contexts, including neurodegeneration and aging. Finally, we highlight that targeting the cytoskeleton-autophagy interaction axis may offer novel therapeutic strategies for related diseases.