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Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease
Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
* Author to whom correspondence should be addressed.
Received: 28 March 2013; in revised form: 1 May 2013 / Accepted: 14 May 2013 / Published: 1 July 2013
Abstract: The endoplasmic reticulum (ER) is an organelle in which newly synthesized secretory and transmembrane proteins are assembled and folded into their correct tertiary structures. However, many of these ER proteins are misfolded as a result of various stimuli and gene mutations. The accumulation of misfolded proteins disrupts the function of the ER and induces ER stress. Eukaryotic cells possess a highly conserved signaling pathway, termed the unfolded protein response (UPR), to adapt and respond to ER stress conditions, thereby promoting cell survival. However, in the case of prolonged ER stress or UPR malfunction, apoptosis signaling is activated. Dysfunction of the UPR causes numerous conformational diseases, including neurodegenerative disease, metabolic disease, inflammatory disease, diabetes mellitus, cancer, and cardiovascular disease. Thus, ER stress-induced signaling pathways may serve as potent therapeutic targets of ER stress-related diseases. In this review, we will discuss the molecular mechanisms of the UPR and ER stress-induced apoptosis, as well as the possible roles of ER stress in several diseases.
Keywords: ER stress; unfolded protein response (UPR); apoptosis; diseases
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Cite This Article
MDPI and ACS Style
Kadowaki, H.; Nishitoh, H. Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease. Genes 2013, 4, 306-333.
Kadowaki H, Nishitoh H. Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease. Genes. 2013; 4(3):306-333.
Kadowaki, Hisae; Nishitoh, Hideki. 2013. "Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease." Genes 4, no. 3: 306-333.