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MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer's disease.(Report)

Baranger, Kevin ; Marchalant, Yannick ; Bonnet, Amandine E. ; Crouzin, Nadine ; Carrete, Alex ; Paumier, Jean - Michel ; Py, Nathalie A. ; Bernard, Anne ; Bauer, Charlotte ; Charrat, Eliane ; Moschke, Katrin ; Seiki, Mothoharu ; Vignes, Michel ; Lichtenthaler, Stefan F. ; Checler, Frederic ; Khrestchatisky, Michel ; Rivera, Santiago

Cellular and Molecular Life Sciences (CMLS), Jan, 2016, Vol.73(1), p.217(20) [Tạp chí có phản biện]

ISSN: 1420-682X ; DOI: 10.1007/s00018-015-1992-1

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  • Nhan đề:
    MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer's disease.(Report)
  • Tác giả: Baranger, Kevin ; Marchalant, Yannick ; Bonnet, Amandine E. ; Crouzin, Nadine ; Carrete, Alex ; Paumier, Jean - Michel ; Py, Nathalie A. ; Bernard, Anne ; Bauer, Charlotte ; Charrat, Eliane ; Moschke, Katrin ; Seiki, Mothoharu ; Vignes, Michel ; Lichtenthaler, Stefan F. ; Checler, Frederic ; Khrestchatisky, Michel ; Rivera, Santiago
  • Chủ đề: Amyloid Beta-Protein -- Analysis ; Genetic Engineering -- Analysis ; Genetically Modified Organisms -- Analysis ; Amyloidosis -- Analysis ; Alzheimer'S Disease -- Analysis ; Resveratrol -- Analysis
  • Là 1 phần của: Cellular and Molecular Life Sciences (CMLS), Jan, 2016, Vol.73(1), p.217(20)
  • Mô tả: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00018-015-1992-1 Byline: Kevin Baranger (1), Yannick Marchalant (1,8), Amandine E. Bonnet (1), Nadine Crouzin (1), Alex Carrete (1), Jean-Michel Paumier (1), Nathalie A. Py (1), Anne Bernard (1), Charlotte Bauer (2), Eliane Charrat (1), Katrin Moschke (3,4), Mothoharu Seiki (5), Michel Vignes (6), Stefan F. Lichtenthaler (3,4,7), Frederic Checler (2), Michel Khrestchatisky (1), Santiago Rivera (1) Keywords: MMP-24; Synaptotoxicity; Neuroprotection; Knockout mouse; Neurodegenerative disease Abstract: Membrane-type 5-matrix metalloproteinase (MT5-MMP) is a proteinase mainly expressed in the nervous system with emerging roles in brain pathophysiology. The implication of MT5-MMP in Alzheimer's disease (AD), notably its interplay with the amyloidogenic process, remains elusive. Accordingly, we crossed the genetically engineered 5xFAD mouse model of AD with MT5-MMP-deficient mice and examined the impact of MT5-MMP deficiency in bigenic 5xFAD/MT5-MMP.sup.-/- mice. At early stages (4 months) of the pathology, the levels of amyloid beta peptide (A[beta]) and its amyloid precursor protein (APP) C-terminal fragment C99 were largely reduced in the cortex and hippocampus of 5xFAD/MT5-MMP.sup.-/-, compared to 5xFAD mice. Reduced amyloidosis in bigenic mice was concomitant with decreased glial reactivity and interleukin-1[beta] (IL-1[beta]) levels, and the preservation of long-term potentiation (LTP) and spatial learning, without changes in the activity of [alpha]-, [beta]- and I[sup.3]-secretases. The positive impact of MT5-MMP deficiency was still noticeable at 16 months of age, as illustrated by reduced amyloid burden and gliosis, and a better preservation of the cortical neuronal network and synaptophysin levels in bigenic mice. MT5-MMP expressed in HEKswe cells colocalized and co-immunoprecipitated with APP and significantly increased the levels of A[beta] and C99. MT5-MMP also promoted the release of a soluble APP fragment of 95 kDa (sAPP95) in HEKswe cells. sAPP95 levels were significantly reduced in brain homogenates of 5xFAD/MT5-MMP.sup.-/- mice, supporting altogether the idea that MT5-MMP influences APP processing. MT5-MMP emerges as a new pro-amyloidogenic regulator of APP metabolism, whose deficiency alleviates amyloid pathology, neuroinflammation and cognitive decline. Author Affiliation: (1) Aix-Marseille Universite, CNRS, NICN UMR 7259, 13344, Marseille, France (2) Labex DistAlz, IPMC UMR 7275 CNRS-UNS, 06560, Valbonne, France (3) German Center for Neurodegenerative Diseases (DZNE) and Neuroproteomics, Munich, Germany (4) Klinikum rechts der Isar, and Institute for Advanced Study, Technische Universitat Munchen (TUM), 81675, Munich, Germany (5) Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan (6) UMR5247 IBMM CNRS University of Montpellier 1 and University of Montpellier 2, 34095, Montepellier, France (7) Munich Cluster for Systems Neurology (SyNergy), 80336, Munich, Germany (8) Psychology Department, Central Michigan University, Mount Pleasant, MI, 48859, USA Article History: Registration Date: 10/07/2015 Received Date: 26/05/2015 Accepted Date: 10/07/2015 Online Date: 23/07/2015 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00018-015-1992-1) contains supplementary material, which is available to authorized users.
  • Ngôn ngữ: English
  • Số nhận dạng: ISSN: 1420-682X ; DOI: 10.1007/s00018-015-1992-1

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