ArticleMolecular neurobiology2019
Influence of Matrix Metallopeptidase 9 on Beta-Amyloid Elimination Across the Blood-Brain Barrier.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- LYVE1 ectodomain shedding blunts lymphatic transmigration and clearance of macrophages during kidney injury.JCI insight · 2026Article
- Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies.Molecular neurobiology · 2026Review
- Exploring the causal relationship and molecular mechanisms between Methyl-4-hydroxybenzoic acid (MEP) and Alzheimer's disease: a mendelian randomization, multi-omics, and network toxicology approach.Toxicology research · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Investigation of the role of miRNA variants in neurodegenerative brain diseases.Frontiers in genetics · 2025Article
- The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.Molecular neurobiology · 2025Review
- Exploring the Mahuang Fuzi Xixin Decoction's mechanism for treating Alzheimer's disease using molecular docking and network pharmacology.Frontiers in aging neuroscience · 2025Article
- PeripheralFrontiers in aging neuroscience · 2025Article
- Metalloproteinase-9 as a Pyroptosis-Hypoxia Synergy Effector Drives Immune Remodeling in Ischemic Stroke: A Multi-Omics Validated Diagnostic Biomarker and Therapeutic Target.International journal of general medicine · 2025Article
- Low-Density Lipoprotein Receptor-Related Protein 1 as a Potential Therapeutic Target in Alzheimer's Disease.Pharmaceutics · 2024Review
- Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Fluid biomarkers in cerebral amyloid angiopathy.Frontiers in neuroscience · 2024Review
- What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation.Mediators of inflammation · 2024Article
- Pharmacological inhibition of receptor protein tyrosine phosphatase β/ζ decreases Aβ plaques and neuroinflammation in the hippocampus of APP/PS1 mice.Frontiers in pharmacology · 2024Article
- Review
- Article
- Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.Aging and disease · 2023Review
- Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.Stroke · 2023Review
- Sex differences in Alzheimer's disease: plasma MMP-9 and markers of disease severity.Alzheimer's research & therapy · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Lipoprotein receptor transport across the blood-brain barrier (BBB) mediates beta-amyloid (Aβ) accumulation in the brain and may be a contributing factor in Alzheimer's disease (AD) pathogenesis. Lipoprotein receptors are susceptible to proteolytic shedding at the cell surface, which precludes the endocytic transport of ligands. A ligand that closely interacts with the lipoprotein receptors is apolipoprotein E (apoE), which exists as three isoforms (apoE2, apoE3, apoE4). Our prior work showed an inverse relationship between lipoprotein receptor shedding and Aβ transport across the BBB, which was apoE-isoform dependent. To interrogate this further, the current studies investigated an enzyme implicated in lipoprotein receptor shedding, matrix metalloproteinase 9 (MMP9). Treatment with MMP9 dose-dependently elevated lipoprotein receptor shedding in brain endothelial cells and freshly isolated mouse cerebrovessels. Furthermore, treatment with a MMP9 inhibitor (SB-3CT) mitigated Aβ-induced lipoprotein receptor shedding in brain endothelial cells and the brains of apoE4 animals. In terms of BBB transit, SB-3CT treatment increased the transport of Aβ across an in vitro model of the BBB. In vivo, administration of SB-3CT to apoE4 animals significantly enhanced Aβ clearance from the brain to the periphery following intracranial administration of Aβ. The current studies show that MMP9 impacts lipoprotein receptor shedding and Aβ transit across the BBB, in an apoE isoform-specific manner. In total, MMP9 inhibition can facilitate Aβ clearance across the BBB, which could be an effective approach to lowering Aβ levels in the brain and mitigating the AD phenotype, particularly in subjects carrying the apoE4 allele.
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Registered trials
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