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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 386 - 394 (9page)
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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 Tg2576mice, 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 β and senile plaque.
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등록된 정보가 없습니다.
참고문헌 (23)
참고문헌 신청
Bence NF / 2001 / Impairment of the ubiquitin-proteasome system by protein aggregation / Science 292 : 1552 ~ 1555
Cosman KM / 2007 / Memantine in the treatment of mild-to-moderate Alzheimer's disease / Expert Opin Pharmacother 8 : 203 ~ 214
Cox JS / 1996 / A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response / Cell 87 : 391 ~ 404
Dugan LL / 1995 / Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate / J Neurosci 15 : 6377 ~ 6388
Ferreiro E / 2006 / An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity / Neurobiol Dis 23 : 669 ~ 678
Cosman KM / 2007 / Memantine in the treatment of mild-to-moderate Alzheimer's disease / Expert Opin Pharmacother 8 : 203 ~ 214
Cox JS / 1996 / A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response / Cell 87 : 391 ~ 404
Dugan LL / 1995 / Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate / J Neurosci 15 : 6377 ~ 6388
Ferreiro E / 2006 / An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity / Neurobiol Dis 23 : 669 ~ 678
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