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Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice.

Authors
Lee, JH; Won, SM; Suh, J; Son, SJ; Moon, GJ; Park, UJ; Gwag, BJ
Citation
Experimental & molecular medicine, 42(5):386-394, 2010
Journal Title
Experimental & molecular medicine
ISSN
1226-36132092-6413
Abstract
The endoplasmic reticulum (ER) stress results from disrupted protein folding triggered by protein mutation or oxidation, reduced proteasome activity, and altered Ca2+ homeostasis. ER stress is accompanied by activation of the unfolded protein response (UPR) and cell death pathway. We examined if the UPR and cell death pathway would be activated in Alzheimer's disease (AD). RT-PCR experiments revealed increased splicing of X-box binding protein-1 (XBP-1), an UPR transcription factor, in AD compared with age-matched control. Among target genes of XBP-1, expression of protein disulfide isomerase (PDI), but not glucose-regulated protein 78 (GRP78), was increased in AD, suggesting disturbed activation of the UPR in AD. C/EBP homologous protein (CHOP), caspase-3, caspase-4, and caspase-12, downstream mediators of cell death pathway, were activated in AD. Neither the UPR nor cell death pathway was induced in aged Tg2576 mice, a transgenic mouse model of Alzheimer's disease that reveals both plaque pathology and some cognitive deficits. The present study suggests that disturbed induction of the UPR and activation of the pro-apoptotic proteins contribute to neuropathological process in AD irrespective of amyloid beta and senile plaque.
MeSH terms
AgedAged, 80 and overAging/genetics*Aging/pathologyAlzheimer Disease/genetics*Alzheimer Disease/metabolismAlzheimer Disease/pathologyAnimalsBlotting, WesternCell Death/genetics*DNA-Binding Proteins/analysis*Endoplasmic Reticulum/geneticsEndoplasmic Reticulum/metabolism*Endoplasmic Reticulum/pathologyHeat-Shock Proteins/analysisHumansImmunohistochemistryMaleMiceMice, TransgenicMiddle AgedProtein Disulfide-Isomerases/analysisStress, Physiological/geneticsTranscription Factors/analysis*Unfolded Protein Response/genetics*
DOI
10.3858/emm.2010.42.5.040
PMID
20368688
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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