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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제20권 제4호
- 발행연도
- 2016.7
- 수록면
- 387 - 397 (11page)
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초록· 키워드
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Neurofibrillary tangles (NFTs) of microtubule-associated protein tau are a pathological hallmark of Alzheimer’s disease (AD). Endoplasmic reticulum (ER) stress has been known to be involved in the pathogenesis of AD. However, the exact role of ER stress in tau pathology has not yet been clearly elucidated. In present study, the possible relationship between tau pathology and ER stress was examined in terms of sorcin, which is a calcium binding protein and plays an important role in calcium homeostasis. Our previous yeast two hybrid study showed that sorcin is a novel tau interacting protein. Caspase-3-cleaved tau (T4C3) showed significantly increased tau-sorcin interaction compared to wild type tau (T4). Thapsigargin-induced ER stress and co-expression of constitutively active GSK3β (GSK3β-S9A) also exhibited significantly increased tau-sorcin interactions. T4C3-expressing cells showed potentiated thapsigargin -induced apoptosis and disruption of intracellular calcium homeostasis compared to T4-expressing cells. Overexpression of sorcin significantly attenuated thapsigargin-induced apoptosis and disruption of calcium homeostasis. In contrary, siRNA-mediated knock-down of sorcin showed significantly increased thapsigargin-induced apoptosis and disruption of calcium homeostasis. These data strongly suggest that sequestration of sorcin by aberrant forms of tau compromises the function of sorcin, such as calcium homeostasis and cellular resistance by ER stress, which may consequently result in the contribution to the progression of AD.
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참고문헌 (45)
참고문헌 신청
Grundke-Iqbal I / 1986 / Abnormal phosphorylation of the microtubule-associated protein tau(tau)in Alzheimer cytoskeletal pathology / Proc Natl Acad Sci U S A 83:4913~4917
Bré MH / 1990 / Effects of brain microtubule-associated proteins on microtubule dynamics and the nucleating activity of centrosomes / Cell Motil Cytoskeleton 15:88~98
Shahani N / 2002 / Functions and malfunctions of the tau proteins / Cell Mol Life Sci 59:1668~1680
Stoothoff WH / 2005 / Tau phosphorylation : physiological and pathological consequences / Biochim Biophys Acta 1739:280~297
Goedert M / 1989 / Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats : differential expression of tau protein mRNAs in human brain / EMBO J 8:393~399
Bré MH / 1990 / Effects of brain microtubule-associated proteins on microtubule dynamics and the nucleating activity of centrosomes / Cell Motil Cytoskeleton 15:88~98
Shahani N / 2002 / Functions and malfunctions of the tau proteins / Cell Mol Life Sci 59:1668~1680
Stoothoff WH / 2005 / Tau phosphorylation : physiological and pathological consequences / Biochim Biophys Acta 1739:280~297
Goedert M / 1989 / Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats : differential expression of tau protein mRNAs in human brain / EMBO J 8:393~399
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