The role of the tubular endoplasmic reticulum in the axonal degeneration associated with neurodegenerative disorders

Neurodegenerative disorders represent a group of aging-related diseases affecting the different parts of the central nervous system. Axonal degeneration is among the leading causes of morbidity and disease progression in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and other neurogenerative disorders. The unique structures of axons may make them particularly vulnerable to internal homeostasis. The axonal endoplasmic reticulum (ER) has emerged as one of the most important hallmarks in those neurodegenerative disorders associated with dysfunction of axonal transport, lipid synthesis, calcium dynamics, and interactions with other organelles. In this review, we summarize the role of tubular ER and its resident proteins in axonal degeneration, which emerges as an early pathological event in the axonal degeneration process. We also discuss the potential relationship between autophagy and tubular ER. With this review, we can consolidate the recent research advances in the role of tubular ER in axonal degeneration associated with several major neurodegenerative disorders and improve our understanding of axon pathophysiology and potential target therapies.