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• W2103997070 endingPage "1687" @default.
• W2103997070 startingPage "1681" @default.
• W2103997070 abstract "Abstract: Our previous studies have demonstrated that perlecan and perlecan-derived glycosaminoglycans (GAGs) not only bind β-amyloid protein (Aβ) 1-40 and 1-42, but are also potent enhancers of Aβ fibril formation and stabilize amyloid fibrils once formed. However, it was not determined which moieties in perlecan heparan sulfate GAG chains may be responsible for the observed effects and whether other GAGs were also capable of a similar enhancement of Aβ fibril formation as observed with perlecan GAGs. In the present study, thioflavin T fluorometry (over a 1-week period) was used to extend our previous studies and to test the hypothesis that the sulfate moiety is critical for the enhancing effects of heparin/heparan sulfate GAGs on Aβ 1-40 fibrillogenesis. This hypothesis was confirmed when removal of all sulfates from heparin (i.e., completely desulfated N-acetylated heparin) led to a complete loss in the enhancement of Aβ fibrillogenesis as demonstrated in both thioflavin T fluorometry and Congo red staining studies. On the other hand, removal of O-sulfate from heparin (i.e., completely desulfated N-sulfated heparin), and to a lesser extent N-sulfate (i.e., N-desulfated N-acetylated heparin), resulted in only a partial loss of the enhancement of Aβ 1-40 fibril formation. These studies indicate that the sulfate moieties of GAGs are critical for enhancement of Aβ amyloid fibril formation. In addition, other sulfated molecules such as chondroitin-4-sulfate, dermatan sulfate, dextran sulfate, and pentosan polysulfate all significantly enhanced (greater than twofold by 3 days) Aβ amyloid fibril formation. These latter findings indicate that deposition and accumulation of other GAGs at sites of Aβ amyloid deposition in Alzheimer’s disease brain may also participate in the enhancement of Aβ amyloidosis." @default.
• W2103997070 created "2016-06-24" @default.
• W2103997070 creator A5019375169 @default.
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• W2103997070 date "2001-12-25" @default.
• W2103997070 modified "2023-10-16" @default.
• W2103997070 title "The Sulfate Moieties of Glycosaminoglycans Are Critical for the Enhancement of β-Amyloid Protein Fibril Formation" @default.
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• W2103997070 doi "https://doi.org/10.1046/j.1471-4159.1999.721681.x" @default.
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