The unfolded protein response is involved in the pathology of Alzheimer's disease.
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.
Kudo
Takashi
T
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
Katayama
Taiichi
T
Imaizumi
Kazunori
K
Yasuda
Yuka
Y
Yatera
Misako
M
Okochi
Masayasu
M
Tohyama
Masaya
M
Takeda
Masatoshi
M
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
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