Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer's Disease
2014 (English)In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, 516028- p.Article, review/survey (Refereed) Published
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.
IdentifiersURN: urn:nbn:se:uu:diva-231495DOI: 10.1155/2014/516028ISI: 000340142600001OAI: oai:DiVA.org:uu-231495DiVA: diva2:744783