title: Unique pharmacological property of ISRIB in inhibition of Aβ-induced neuronal cell death.
abstract: A pharmacological approach to ameliorate Alzheimer's disease (AD) has not yet been established. In the present study, we investigated the pharmacological characteristics of the recently identified memory-enhancing compound, ISRIB for the amelioration of AD. ISRIB potently attenuated amyloid β-induced neuronal cell death at concentrations of 12.5-25 nM, but did not inhibit amyloid β production in the HEK293T cell line expressing the amyloid precursor protein (APP). These results suggest that ISRIB possesses the unique pharmacological property of attenuating amyloid β-induced neuronal cell death without affecting amyloid β production.
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: toruh@hiroshima-u.ac.jp.
authors: Toru
authors: T
authors: Hosoi
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Mai
authors: M
authors: Kakimoto
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Keigo
authors: K
authors: Tanaka
authors: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Jun
authors: J
authors: Nomura
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: ozawak@hiroshima-u.ac.jp.
authors: Koichiro
authors: K
authors: Ozawa
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D051701:Activating Transcription Factor 4 / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D003514:Cyclohexylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000599093:2-(4-chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetamido)cyclohexyl)acetamide; C497109:ATF4 protein, human; D000081:Acetamides; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003514:Cyclohexylamines; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D051701:Activating Transcription Factor 4
keywords: Alzheimer's disease; Amyloid β; ISRIB