ER Stress and Disease: Toward Prevention and Treatment

Kaneko Masayuki

Imaizumi Kazunori

Saito Atsushi

Kanemoto Soshi

Asada Rie

Matsuhisa Koji

Ohtake Yosuke

Biological and Pharmaceutical Bulletin

Secretory and membrane proteins are synthesized in ribosomes, then mature in the endoplasmic reticulum (ER), but if ER function is impaired, immature defective proteins accumulate in the ER. This situation is called ER stress: in response, a defensive mechanism called the unfolded protein response (UPR) is activated in cells to reduce the defective proteins. During the UPR, the ER transmembrane sensor molecules inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), and RNA-dependent protein kinase (PKR)-like ER kinase (PERK) are activated, stress signals are transduced to the outside of the ER, and various cell responses, including gene induction, occur. In ER-associated degradation (ERAD), one type of UPR, defective proteins are eventually expelled from the ER and degraded in the cytoplasm through the ubiquitin proteasome system. Since ER stress has been reported to have relationships with neurodegenerative diseases, diabetes, metabolic syndromes, and cancer, it is the focus of increased attention from the perspectives of elucidating pathogenic mechanisms, and in the development of therapeutics.

endoplasmic reticulum stress

unfolded protein response

neurodegenerative disease

diabetes

metabolic syndrome

cancer

医学 [ 490 ]

英語

The Pharmaceutical Society of Japan

© 2018 The Pharmaceutical Society of Japan

[ISSN] 0918-6158

[ISSN] 1347-5215

[NCID] AA10885497

[DOI] 10.1248/bpb.b17-00342

[DOI] https://doi.org/10.1248/bpb.b17-00342