Protein Misfolding Disorders: A Trip into the ER

Indexed in: Scopus, EBSCO.

Neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Prion-related disorders (PrD) and Huntington’s disease (HD) share a ...
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ER Quality Control, ER Stress-Induced Apoptosis, and Neurodegenerative Diseases

Pp. 94-102 (9)

Hideki Nishitoh, Hisae Kadowaki, Kohsuke Takeda and Hidenori Ichijo

Abstract

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.

Affiliation:

Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.