ArticleThe Journal of biological chemistry2015
Overexpression of heparanase lowers the amyloid burden in amyloid-β precursor protein transgenic mice.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- Brain Region-Specific Accumulation of Amyloidosis-Associated Proteins in Postmortem Brain Tissues of Alzheimer's Disease Patients.Molecular neurobiology · 2025Article
- Article
- Article
- Vascular Heparan Sulfate and Amyloid-β in Alzheimer's Disease Patients.International journal of molecular sciences · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Global impact of proteoglycan science on human diseases.iScience · 2023Review
- 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
- Heparin mimetics as potential intervention for COVID-19 and their bio-manufacturing.Synthetic and systems biotechnology · 2023Review
- Basal lamina changes in neurodegenerative disorders.Molecular neurodegeneration · 2021Review
- Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology.Molecular neurodegeneration · 2021Review
- Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer's disease.Acta neuropathologica communications · 2021Article
- Glycosaminoglycans in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2021Review
- Heparan Sulfate Structure Affects Autophagy, Lifespan, Responses to Oxidative Stress, and Cell Degeneration inG3 (Bethesda, Md.) · 2020Article
- Targeting soluble tumor necrosis factor as a potential intervention to lower risk for late-onset Alzheimer's disease associated with obesity, metabolic syndrome, and type 2 diabetes.Alzheimer's research & therapy · 2019Article
- Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression.Scientific reports · 2019Article
- Glycosaminoglycans have variable effects on α-synuclein aggregation and differentially affect the activities of the resulting amyloid fibrils.The Journal of biological chemistry · 2018Article
- Heparan Sulfate Proteoglycans as Relays of Neuroinflammation.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparan sulfate (HS) and HS proteoglycans (HSPGs) colocalize with amyloid-β (Aβ) deposits in Alzheimer disease brain and in Aβ precursor protein (AβPP) transgenic mouse models. Heparanase is an endoglycosidase that specifically degrades the unbranched glycosaminoglycan side chains of HSPGs. The aim of this study was to test the hypothesis that HS and HSPGs are active participators of Aβ pathogenesis in vivo. We therefore generated a double-transgenic mouse model overexpressing both human heparanase and human AβPP harboring the Swedish mutation (tgHpa*Swe). Overexpression of heparanase did not affect AβPP processing because the steady-state levels of Aβ1-40, Aβ1-42, and soluble AβPP β were the same in 2- to 3-month-old double-transgenic tgHpa*Swe and single-transgenic tgSwe mice. In contrast, the Congo red-positive amyloid burden was significantly lower in 15-month-old tgHpa*Swe brain than in tgSwe brain. Likewise, the Aβ burden, measured by Aβx-40 and Aβx-42 immunohistochemistry, was reduced significantly in tgHpa*Swe brain. The intensity of HS-stained plaques correlated with the Aβx-42 burden and was reduced in tgHpa*Swe mice. Moreover, the HS-like molecule heparin facilitated Aβ1-42-aggregation in an in vitro Thioflavin T assay. The findings suggest that HSPGs contribute to amyloid deposition in tgSwe mice by increasing Aβ fibril formation because heparanase-induced fragmentation of HS led to a reduced amyloid burden. Therefore, drugs interfering with Aβ-HSPG interactions might be a potential strategy for Alzheimer disease treatment.
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Registered trials
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