Tubular ER dysfunction in neurodegenerative diseases.

Endoplasmic reticulum (ER) is the largest secretory organelle, and it regulates diverse cellular processes to support neuronal growth, development, and maintenance during the lifespan. Structural alterations to the ER network affect a multitude of functions and downstream events, which result in abnormalities in neuronal maintenance and neuronal death. Morphological and functional abnormalities in the tubular domain of ER or in tubular ER proteins have been linked to several major neurodegenerative diseases, including Alzheimer's disease (AD) and hereditary spastic paraplegias (HSPs). Tubular ER dysfunction in neurodegenerative diseases is manifested by elevated expression, abnormal aggregation, haplo-insufficiency, or functional deficiency in multiple ER tubule-shaping proteins. This review aims to highlight the involvement of ER tubule shaping and networking proteins that cause tubular ER dysfunction in AD and HSPs. The discussion of this review will also highlight the functional necessity of an integrated tubular ER network for axonal maintenance.