| Title |
MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer’s disease
|
|---|---|
| Published in |
Cellular and Molecular Life Sciences, July 2015
|
| DOI | 10.1007/s00018-015-1992-1 |
| Pubmed ID | |
| Authors |
Kévin Baranger, Yannick Marchalant, Amandine E. Bonnet, Nadine Crouzin, Alex Carrete, Jean-Michel Paumier, Nathalie A. Py, Anne Bernard, Charlotte Bauer, Eliane Charrat, Katrin Moschke, Mothoharu Seiki, Michel Vignes, Stefan F. Lichtenthaler, Frédéric Checler, Michel Khrestchatisky, Santiago Rivera |
| 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(-/-) 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. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 20% |
| United States | 1 | 20% |
| Portugal | 1 | 20% |
| United Kingdom | 1 | 20% |
| Unknown | 1 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 1% |
| Unknown | 92 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 20 | 22% |
| Researcher | 16 | 17% |
| Student > Master | 14 | 15% |
| Student > Bachelor | 8 | 9% |
| Student > Postgraduate | 6 | 6% |
| Other | 13 | 14% |
| Unknown | 16 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 20 | 22% |
| Neuroscience | 13 | 14% |
| Biochemistry, Genetics and Molecular Biology | 12 | 13% |
| Psychology | 7 | 8% |
| Chemistry | 6 | 6% |
| Other | 11 | 12% |
| Unknown | 24 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 June 2018.
All research outputs
#2,341,912
of 23,794,258 outputs
Outputs from Cellular and Molecular Life Sciences
#298
of 4,151 outputs
Outputs of similar age
#30,776
of 265,054 outputs
Outputs of similar age from Cellular and Molecular Life Sciences
#4
of 60 outputs
Altmetric has tracked 23,794,258 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,151 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has done particularly well, scoring higher than 99% of its peers.
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We're also able to compare this research output to 60 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.