Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease.
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Watanabe N, Araki W, Chui DH, Makifuchi T, Ihara Y, Tabira T
Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease.
FASEB J. 2004 Jun;18(9):1013-5. Epub 2004 Apr 14.
- PubMed ID
- 15084524 [ View in PubMed]
- Abstract
Previous studies have suggested that heparan sulfate proteoglycans (HSPGs) play a role in deposition of beta-amyloid protein (Abeta) in the Alzheimer's disease (AD) brain. In the present study, we demonstrated that glypican-1 can bind fibrillar Abeta, and the binding is mainly mediated by heparan sulfate (HS) chains. Further analysis revealed that glypican-1 is the major HSPG localized in detergent-insoluble glycosphingolipid-enriched (DIG) domains where all machineries for Abeta production exist and Abeta is accumulated as monomeric and oligomeric forms. Immunohistochemical studies demonstrated that glypican-1 is localized in primitive plaques as well as classic plaques. Moreover, overexpression of glypican-1 and amyloid precursor protein in SH-SY5Y cells resulted in reduced cell viability and made cells more susceptible to thapsigargin-induced stress and Abeta toxicity. The results raise the possibility that glypican-1 interacts with oligomerized or polymerized Abeta in such a specific compartment as DIG, resulting not only in amyloid deposition in senile plaques of AD brain, but also in accelerating neuronal cell death in response to stress and Abeta.