ArticleFrontiers in aging neuroscience2014
Differential spatio-temporal regulation of MMPs in the 5xFAD mouse model of Alzheimer's disease: evidence for a pro-amyloidogenic role of MT1-MMP.
Article in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 74 citations in OpenAlex.
- MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity.Cell discovery · 2025Article
- Impaired Oxidative Stress Markers and Activities of Matrix Metalloproteinases in Plasma of Patients with Alzheimer's Disease, Emphasizing Sex andInternational journal of molecular sciences · 2025Article
- 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
- Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A New Cell Model Overexpressing sTGFBR3 for Studying Alzheimer's DiseaseCurrent pharmaceutical design · 2024Article
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Sex-specific associations of matrix metalloproteinases in Alzheimer's disease.Biology of sex differences · 2023Article
- Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model.iScience · 2023Article
- Article
- Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease.Inflammation and regeneration · 2023Article
- Metal Complexes as Promising Matrix Metalloproteinases Regulators.International journal of molecular sciences · 2023Review
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Matrix Metalloproteases from Adipose Tissue-Derived Stromal Cells Are Spatiotemporally Regulated by Hydrogel Mechanics in a 3D Microenvironment.Bioengineering (Basel, Switzerland) · 2022Article
- 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 role of neutrophils in the dysfunction of central nervous system barriers.Frontiers in aging neuroscience · 2022Review
- Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice.Experimental neurobiology · 2021Article
- MMP9 modulation improves specific neurobehavioral deficits in a mouse model of Alzheimer's disease.BMC neuroscience · 2021Article
- Blood-brain barrier dysfunction as a potential therapeutic target for neurodegenerative disorders.Archives of pharmacal research · 2021Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinases (MMPs) are pleiotropic endopeptidases involved in a variety of neurodegenerative/neuroinflammatory processes through their interactions with a large number of substrates. Among those, the amyloid precursor protein (APP) and the beta amyloid peptide (Aβ) are largely associated with the development of Alzheimer's disease (AD). However, the regulation and potential contribution of MMPs to AD remains unclear. In this study, we investigated the evolution of the expression of MMP-2, MMP-9, and membrane-type 1-MMP (MT1-MMP) in the hippocampus at different stages of the pathology (asymptomatic, prodromal-like and symptomatic) in the 5xFAD transgenic mouse AD model. In parallel we also followed the expression of functionally associated factors. Overall, the expression of MMP-2, MMP-9, and MT1-MMP was upregulated concomitantly with the tissue inhibitor of MMPs-1 (TIMP-1) and several markers of inflammatory/glial response. The three MMPs exhibited age- and cell-dependent upregulation of their expression, with MMP-2 and MMP-9 being primarily located to astrocytes, and MT1-MMP to neurons. MMP-9 and MT1-MMP were also prominently present in amyloid plaques. The levels of active MT1-MMP were highly upregulated in membrane-enriched fractions of hippocampus at 6 months of age (symptomatic phase), when the levels of APP, its metabolites APP C-terminal fragments (CTFs), and Aβ trimers were the highest. Overexpression of MT1-MMP in HEK cells carrying the human APP Swedish mutation (HEKswe) strongly increased β-secretase derived C-terminal APP fragment (C99) and Aβ levels, whereas MMP-2 overexpression nearly abolished Aβ production without affecting C99. Our data consolidate the emerging idea of a regulatory interplay between MMPs and the APP/Aβ system, and demonstrate for the first time the pro-amyloidogenic features of MT1-MMP. Further investigation will be justified to evaluate this MMP as a novel potential therapeutic target in AD.
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