The endoplasmic reticulum (ER) is the intracellular organelle in which newly synthesized
secretory and transmembrane proteins achieve proper structure as a result of post-translational
modification, folding, and oligomerization. However, many of these proteins are malfolded (unfolded
or misfolded) as a result of various intracellular or extracellular stimuli. ER stress is caused by
disturbances of ER function with the accumulation of malfolded proteins and alterations in calcium
homeostasis. To restore ER function, cells possess a highly specific ER quality control system to
increase the capacity of protein folding and to reduce the amount of malfolded proteins in the ER. In
case of prolonged ER stress or malfunction of the ER quality control system, apoptosis signaling is
activated. ER stress-induced apoptosis has recently been implicated in human neurodegenerative
diseases such as Alzheimer disease, Parkinson disease, polyglutamine diseases, and amyotrophic
lateral sclerosis. This review summarizes the molecular mechanisms of the ER quality control system
and ER stress-induced apoptosis and the possible roles of ER stress in neurodegenerative diseases.
