[A molecular chaperone inducer as potential therapeutic agent for neurodegenerative disease].
Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases. In a screen for compounds that induce the ER-mediated chaperone BiP/GRP 78 (BiP), we identified BiP inducer X (BIX). BIX induced BiP only, in a dose-dependent manner, without induction of other molecules involved in the ER stress response. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Taken together, BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress.
Kudo
Takashi
T
Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2 Yamadaoka, Suita, 565-0871 Japan. kudo@psy.med.osaka-u.ac.jp
Imaizumi
Kazunori
K
Hara
Hideaki
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger