ArticleJournal of Alzheimer's disease : JAD2014
Perlecan domain V inhibits amyloid-β induced brain endothelial cell toxicity and restores angiogenic function.
Article in Journal of Alzheimer's disease : JAD, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- The glycosaminoglycan chains of perlecan regulate the perivascular fluid transport.Fluids and barriers of the CNS · 2025Article
- Recombinant Human Perlecan DV and Its LG3 Subdomain Are Neuroprotective and Acutely Functionally Restorative in Severe Experimental Ischemic Stroke.Translational stroke research · 2023Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Perlecan: a review of its role in neurologic and musculoskeletal disease.Frontiers in physiology · 2023Review
- All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease.Neural regeneration research · 2022Review
- Basal lamina changes in neurodegenerative disorders.Molecular neurodegeneration · 2021Review
- Neuroinflammation and fibrosis in stroke: The good, the bad and the ugly.Journal of neuroimmunology · 2020Review
- Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia.International journal of molecular sciences · 2020Review
- Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules.Frontiers in pharmacology · 2019Review
- Epidermal growth factor preventsHeliyon · 2017Article
- Molecular and genetic inflammation networks in major human diseases.Molecular bioSystems · 2016Review
- The potential role of perlecan domain V as novel therapy in vascular dementia.Metabolic brain disease · 2015Review
- Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1-40-induced toxicity.Acta pharmaceutica Sinica. B · 2015Article
- Juvenile traumatic brain injury induces long-term perivascular matrix changes alongside amyloid-beta accumulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In Alzheimer's disease (AD), amyloid-β (Aβ) deposits in the cerebrovasculature can result in neurovascular dysfunction and/or cerebral amyloid angiopathy. The accumulation of Aβ in blood vessels can cause endothelial cell damage, resulting in impaired Aβ clearance by the blood-brain barrier. Additionally, impaired endothelial cell function can result in decreased angiogenesis in the brains of AD patients, affecting cognitive function. VEGF is a crucial mediator of angiogenesis and is deficient in AD brains thus promoting angiogenesis could be an important component of successful AD treatment. The C-terminal portion of the extracellular matrix proteoglycan perlecan, Domain V (DV), promotes brain-derived endothelial cell proliferation and is proangiogenic in that it increases VEGFR2 expression and production of VEGF. In this study, we show that Aβ25-35 reduces proliferation of a mouse brain microvascular endothelial cell line (MBEC) in vitro and that DV and mouse LG3 (C-terminal fragment of DV) block these effects of Aβ25-35. Additionally, we show that DV restores the ability of MBECs to form tube-like structures on Matrigel in the presence of Aβ25-35 and that this is α5β1 dependent. Interestingly, the reduction in tube-like structure formation by Aβ25-35 was not due to endothelial cell death, suggesting that Aβ25-35 induces the downregulation of a cell surface molecule required for adhesion events critical to the angiogenic process. We propose a model suggesting that DV works through both the α5β1 integrin receptor and VEGFR2 to increase VEGF production, causing competition with Aβ25-35 for VEGFR2 binding, thus ultimately increasing VEGF expression and restoring angiogenesis. This supports DV as a potential anti-amyloid therapy.
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Registered trials
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.