Advances in Aggrephagy: Mechanisms, Disease Implications, and Therapeutic Strategies

Abstract

The accumulation of misfolded proteins within cells leads to the formation of protein aggregates that disrupt normal cellular functions and contribute to a range of human pathologies, notably neurodegenerative disorders. Consequently, the investigation into the mechanisms of aggregate formation and their subsequent clearance is of considerable importance for the development of therapeutic strategies. The clearance of protein aggregates is predominantly achieved via the autophagy-lysosomal pathway, a process known as aggrephagy. In this pathway, autophagosome biogenesis and lysosomal digestion provide necessary conditions for the clearance of protein aggregates, while autophagy receptors such as P62, NBR1, TAX1BP1, TOLLIP, and CCT2 facilitate the recognition of protein aggregates by the autophagy machinery, playing a pivotal role in their degradation. This review will introduce the mechanisms of aggregate formation, progression, and degradation, with particular emphasis on advances in aggrephagy, providing insights for aggregates-related diseases and the development of novel therapeutic strategies.

Keywords: aggrephagy; aggrephagy receptors; autophagy; neurodegeneration; protein aggregates.