https://scholars.lib.ntu.edu.tw/handle/123456789/507592
標題: | Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia | 作者: | Yang C.-N. Wu M.-F. Liu C.-C. Jung W.-H. Chang Y.-C. Lee W.-P. Shiao Y.-J. Wu C.-L. HORNG-HUEI LIOU SZE-KWAN LIN CHIH-CHIANG CHAN |
公開日期: | 2017 | 出版社: | Oxford University Press | 卷: | 26 | 期: | 20 | 起(迄)頁: | 3909-3921 | 來源出版物: | Human Molecular Genetics | 摘要: | Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells. CTGF enhanced extracellular Aβ degradation via membrane-bound matrix metalloproteinase-14 (MMP14) in glia and extracellular MMP13 in neurons. In the brain of a Drosophila AD model, glial-expression of CTGF reduced Aβ deposits, improved locomotor function, and rescued memory deficits. Neuroprotective potential of CTGF against Aβ42-induced photoreceptor degeneration was disrupted through silencing MMPs. Therefore, CTGF may represent a node for potential AD therapeutics as it intervenes in glia-neuron communication via specific MMPs to alleviate Aβ neurotoxicity in the central nervous system. ? The Author 2017. Published by Oxford University Press. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031742328&doi=10.1093%2fhmg%2fddx278&partnerID=40&md5=b65a03cd9f447b356e17ff232cf8d4fe https://scholars.lib.ntu.edu.tw/handle/123456789/507592 |
ISSN: | 0964-6906 | DOI: | 10.1093/hmg/ddx278 | SDG/關鍵字: | amyloid beta protein; collagenase 3; connective tissue growth factor; matrix metalloproteinase 14; amyloid beta protein; connective tissue growth factor; matrix metalloproteinase 14; MMP14 protein, human; neuroprotective agent; peptide fragment; Alzheimer disease; amnesia; animal experiment; animal model; Article; astrocyte; controlled study; down regulation; enzyme linked immunosorbent assay; fruit fly model; gene silencing; glia cell; human; human cell; immunohistochemistry; in vitro study; locomotion; microglia; molecular cloning; molecular pathology; nerve cell; nerve degeneration; neuroblastoma cell; neuropathology; neuroprotection; neurotoxicity; nonhuman; photoreceptor; primary cell; priority journal; protein degradation; protein expression; protein function; protein secretion; protein targeting; protein transport; SH-SY5Y cell line; upregulation; Western blotting; Alzheimer disease; amyloid plaque; animal; brain; disease model; Drosophila; glia; metabolism; mouse; nerve cell; physiology; rat; toxicity and intoxication; transgenic animal; Alzheimer Disease; Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Astrocytes; Brain; Connective Tissue Growth Factor; Disease Models, Animal; Drosophila; Humans; Matrix Metalloproteinase 14; Mice; Neuroglia; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; Peptide Fragments; Plaque, Amyloid; Rats |
顯示於: | 生理學科所 |
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