title: The unfolded protein response is involved in the pathology of Alzheimer's disease.
abstract: The endoplasmic reticulum (ER) performs the synthesis, posttranslational modification, and proper folding of proteins. A variety of conditions can be ER stress, causing the accumulation of unfolding or misfolding proteins in the ER. Eukaryotic cells have three different mechanisms for dealing with an accumulation of unfolded proteins in the ER known as the unfolded protein response (UPR): transcriptional induction, translational attenuation, and degradation. This paper focuses on the relationship between UPR and the pathogenesis of AD. Our results indicate a new mechanism by which PS1 mutations may affect the sensing of ER stress. Experimental manipulation of IRE1, PERK, or eIF2alpha phosphorylation or GRP78 expression might allow the development of therapeutic strategies for FAD.
authors.affiliation: Department of Psychiatry and Behavioral Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kudo@psy.med.osaka-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Misako
authors.initials: M
authors.lastname: Yatera
authors.forename: Masayasu
authors.initials: M
authors.lastname: Okochi
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001324:Autoantigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008959:Models, Neurological; D018832:Molecular Chaperones / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger