Advances in Research on Endoplasmic Reticulum-Associated Degradation Mechanisms in Neurodegenerative Diseases

The endoplasmic reticulum protein quality control system-comprising endoplasmic reticulum-associated degradation (ERAD), the unfolded protein response (UPR), and ER-phagy-serves as a crucial mechanism for maintaining protein homeostasis within the endoplasmic reticulum (ER) of eukaryotic cells. As a crucial pathway of recognition, transport, and degradation of misfolded proteins, ERAD dysfunction results in the excessive accumulation of aberrant proteins, thereby disrupting normal cellular physiology and ultimately leading to necrosis or apoptosis. It is reported that the occurrence and development of central and peripheral neurodegenerative diseases are closely related to the dysfunction of misfolded protein degradation. Many components within the ERAD pathway may play essential roles in these pathological processes. This review provides an overview of the ERAD processes, its regulatory mechanisms, and its involvement in the pathogenesis and potential treatment of neurodegenerative diseases, aiming to offer theoretical insight for future research on the specific roles of ERAD in different neurodegenerative diseases.