https://scholars.lib.ntu.edu.tw/handle/123456789/569463
標題: | FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines | 作者: | Liu F.-L. Liu T.-Y. FAN-LU KUNG |
關鍵字: | AICD (APP intracellular domain); Alzheimer's disease; FK506; FKBPs | 公開日期: | 2014 | 卷: | 39 | 期: | 1 | 起(迄)頁: | 85-95 | 來源出版物: | Journal of Biosciences | 摘要: | One of the pathological hallmarks of Alzheimer's disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (Aβ), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimer's disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the subcellular localization of APP, upon FKBP12 overexpression. This FKBP12-overexpression-induced effect was reverted by FK506. These findings support our hypothesis that FKBP12 may participate in the regulation of APP processing. FKBP12 overexpression may lead to the stabilization of a certain isomer (presumably the cis form) of the Thr668-Pro669 peptide bond in AICD, therefore change its affinity to flotillin-1 or other raft-associated proteins, and eventually change the localization pattern and cause a shift in the proteolytic processing of APP. ? 2014 Indian Academy of Sciences. |
URI: | 2-s2.0-84896038572 https://scholars.lib.ntu.edu.tw/handle/123456789/569463 |
ISSN: | 2505991 | DOI: | 10.1007/s12038-013-9400-1 | SDG/關鍵字: | amyloid precursor protein; fk 506 binding protein; fk 506 binding protein 12; messenger RNA; unclassified drug; cell organelle; disease; peptide; protein; Alzheimer disease; article; binding affinity; binding site; cellular distribution; controlled study; disease activity; human; human cell; molecular dynamics; molecular pathology; protein binding; protein determination; protein expression; protein function; protein localization; protein phosphorylation; protein processing; protein protein interaction; signal transduction; Alzheimer Disease; Amyloid beta-Protein Precursor; Humans; Membrane Proteins; Protein Processing, Post-Translational; Tacrolimus; Tacrolimus Binding Protein 1A |
顯示於: | 藥學系 |
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