Abstract
Chaperones are proteins that assist the correct folding of other protein clients either when the clients are being synthesized or at their functional localities. Chaperones are responsible for certain diseases. The sigma-1 receptor is recently identified as a receptor chaperone whose activity can be activated/deactivated by specific ligands. Under physiological conditions, the sigma-1 receptor chaperones the functional IP3 receptor at the endoplasmic reticulum and mitochondrion interface to ensure proper Ca2+ signaling from endoplasmic reticulum into mitochondrion. However, under pathological conditions whereby cells encounter enormous stress that results in the endoplasmic reticulum losing its global Ca2+ homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. Thus, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress. The sigma-1 receptor has been implicated in many diseases including addiction, pain, depression, stroke, and cancer. Whether the chaperone activity of the sigma-1 receptor attributes to those diseases awaits further investigation.
Keywords: Sigma receptor, chaperone, ER stress, mitochondrion, nucleus, calcium signaling, IP3 receptor, MAM
Central Nervous System Agents in Medicinal Chemistry
Title: Sigma-1 Receptor Chaperones and Diseases
Volume: 9 Issue: 3
Author(s): Shang-Yi Tsai, Teruo Hayashi, Tomohisa Mori and Tsung-Ping Su
Affiliation:
Keywords: Sigma receptor, chaperone, ER stress, mitochondrion, nucleus, calcium signaling, IP3 receptor, MAM
Abstract: Chaperones are proteins that assist the correct folding of other protein clients either when the clients are being synthesized or at their functional localities. Chaperones are responsible for certain diseases. The sigma-1 receptor is recently identified as a receptor chaperone whose activity can be activated/deactivated by specific ligands. Under physiological conditions, the sigma-1 receptor chaperones the functional IP3 receptor at the endoplasmic reticulum and mitochondrion interface to ensure proper Ca2+ signaling from endoplasmic reticulum into mitochondrion. However, under pathological conditions whereby cells encounter enormous stress that results in the endoplasmic reticulum losing its global Ca2+ homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. Thus, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress. The sigma-1 receptor has been implicated in many diseases including addiction, pain, depression, stroke, and cancer. Whether the chaperone activity of the sigma-1 receptor attributes to those diseases awaits further investigation.
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Cite this article as:
Tsai Shang-Yi, Hayashi Teruo, Mori Tomohisa and Su Tsung-Ping, Sigma-1 Receptor Chaperones and Diseases, Central Nervous System Agents in Medicinal Chemistry 2009; 9 (3) . https://dx.doi.org/10.2174/1871524910909030184
DOI https://dx.doi.org/10.2174/1871524910909030184 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
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