ArticleCellular and molecular life sciences : CMLS2016
MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer's disease.
Article in Cellular and molecular life sciences : CMLS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 108 citations in OpenAlex.
- Structure-Guided Discovery of a Nonpeptidic MT5-MMP Inhibitor.ACS medicinal chemistry letters · 2026Article
- Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026Article
- Copy number loss Of APP cause thoracic aortic dissection.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Membrane-Type 5 Matrix Metalloproteinase (MT5-MMP): Background and Proposed Roles in Normal Physiology and Disease.Biomolecules · 2025Review
- Implications of Mucin-TypeMolecules (Basel, Switzerland) · 2025Review
- The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.Molecular neurobiology · 2025Review
- Suppression of MT5-MMP Reveals Early Modulation of Alzheimer's Pathogenic Events in Primary Neuronal Cultures of 5xFAD Mice.Biomolecules · 2024Article
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- A global view of aging and Alzheimer's pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains.Nature genetics · 2023Article
- The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.International journal of molecular sciences · 2023Article
- The η-secretase-derived APP fragment ηCTF is localized in Golgi, endosomes and extracellular vesicles and contributes to Aβ production.Cellular and molecular life sciences : CMLS · 2023Article
- 30th Annual GPPharmaceuticals (Basel, Switzerland) · 2023Article
- Matrix metalloproteinases as biomarkers and therapeutic targets in colitis-associated cancer.Frontiers in oncology · 2023Review
- Aminopeptidase A and dipeptidyl peptidase 4: a pathogenic duo in Alzheimer's disease?Neural regeneration research · 2022Article
- The Role of Extracellular Matrix in Human Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- The amyloid precursor protein: a converging point in Alzheimer's disease.Molecular neurobiology · 2022Review
- Parkin as a Molecular Bridge Linking Alzheimer's and Parkinson's Diseases?Biomolecules · 2022Review
- MT5-MMP promotes neuroinflammation, neuronal excitability and Aβ production in primary neuron/astrocyte cultures from the 5xFAD mouse model of Alzheimer's disease.Journal of neuroinflammation · 2022Article
- Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.Cellular and molecular life sciences : CMLS · 2022Review
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.