skip to main content
Ngôn ngữ:
Giới hạn tìm kiếm: Giới hạn tìm kiếm: Dạng tài nguyên Hiển thị kết quả với: Hiển thị kết quả với: Chỉ mục

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

Baranger , Kévin ; 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 , Frédéric ; Khrestchatisky , Michel ; Rivera , Santiago

Cellular and molecular life sciences, 2016, Vol.73(1), pp.217-236 [Tạp chí có phản biện]

ISSN: 1420-682X

Truy cập trực tuyến

Trích dẫn Trích dẫn bởi
  • 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
  • Tác giả: Baranger , Kévin ; 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 , Frédéric ; Khrestchatisky , Michel ; Rivera , Santiago
  • Chủ đề: Cortex ; Proteinases ; Metabolism ; Animal Models ; Learning ; Pathophysiology ; Mice ; Amyloidosis ; Interleukin-1beta ; Alzheimer Disease ; Hippocampus ; Transgenic Animals ; Neural Networks ; Amyloid
  • Là 1 phần của: Cellular and molecular life sciences, 2016, Vol.73(1), pp.217-236
  • Mô tả: 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⁻/⁻ mice. At early stages (4 months) of the pathology, the levels of amyloid beta peptide (Aβ) and its amyloid precursor protein (APP) C-terminal fragment C99 were largely reduced in the cortex and hippocampus of 5xFAD/MT5-MMP⁻/⁻, compared to 5xFAD mice. Reduced amyloidosis in bigenic mice was concomitant with decreased glial reactivity and interleukin-1β (IL-1β) levels, and the preservation of long-term potentiation (LTP) and spatial learning, without changes in the activity of α-, β- and γ-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 Aβ 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⁻/⁻ 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. ; p. 217-236.
  • Ngôn ngữ: English
  • Số nhận dạng: ISSN: 1420-682X

Đang tìm Cơ sở dữ liệu bên ngoài...