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Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer's Disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2014 (English)In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, 516028- p.Article, review/survey (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive loss of memory and cognitive dysfunctions. A central pathological event of AD is accumulation and deposition of cytotoxic amyloid-beta peptide (A beta) in the brain parenchyma. Heparan sulfate proteoglycans (HSPGs) and the side chains heparan sulfate (HS) are found associated with A beta deposits in the brains of AD patients and transgenic animal models of AD. A growing body of evidence from in vitro and in vivo studies suggests functional roles of HSPG/HS in A beta pathogenesis. Although the question of "how and why HSPG/HS is codeposited with A beta?" still remains, it is within reach to understand the mechanisms of the events. Recent progress by immunohistochemical examination with advanced antibodies shed light on molecular structures of HS codeposited with A beta Several recent reports have provided important new insights into the roles of HSPG in A beta pathogenesis. Particularly, experiments on mouse models revealed indispensible functions of HSPG in modulating A beta-associated neuroinflammation and clearance of A beta from the brain. Application of molecules to interfere with the interaction between HS and A beta peptides has demonstrated beneficial effects on AD mouse models. Elucidating the functions of HSPG/HS in A beta deposition and toxicity is leading to further understanding of the complex pathology of AD. The progress is encouraging development of new treatments for AD by targeting HS-A beta interactions.

Place, publisher, year, edition, pages
2014. 516028- p.
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:uu:diva-231495DOI: 10.1155/2014/516028ISI: 000340142600001OAI: oai:DiVA.org:uu-231495DiVA: diva2:744783
Available from: 2014-09-08 Created: 2014-09-08 Last updated: 2017-12-05Bibliographically approved

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