Inhibition of Apolipoprotein E- Related Neurotoxicity by Glycosaminoglycans and their Oligosaccharides

Authors
Bazin, H.G.
Marques, Marcos A.
Owens, Albert P.
Linhardt, Robert J.
Crutcher, Keith A.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2002-06-25
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Inhibition of Apolipoprotein E- Related Neurotoxicity by Glycosaminoglycans and their Oligosaccharides, H.G. Bazin, M.A. Marques, A.P. Owens, R.J. Linhardt, K.A. Krutcher, Biochemistry, 41, 8203-8211, 2002.
Abstract
Apolipoprotein E (apoE) has been genetically linked to late-onset Alzheimer's disease (AD). The role of this lipid-transport protein in AD remains to be established. One hypothesis is that apoE, particularly the apoE4 isoform, may have neurotoxic effects as demonstrated using apoE-related synthetic peptides and the N-terminal fragment of apoE. ApoE is a heparan-sulfate binding protein, and apoE peptide neurotoxicity can be blocked by heparin and prevented by degrading heparan sulfate or inhibiting its biosynthesis. The possibility that heparin inhibition of toxicity is mediated by a specific oligosaccharide sequence was investigated using a bioassay to determine the inhibition of apoE peptide toxicity by glycosaminoglycans and purified glycosaminoglycan oligosaccharides. Studies on modified heparins showed that the presence of N-sulfo groups and either 2- or 6-O sulfo groups were required for inhibition of toxicity. Heparin oligosaccharides with eight or more saccharide residues with seven O-sulfo groups and four N-sulfo groups exhibited potent inhibition. Larger oligosaccharides, and heparin and heparan sulfate polymers, afforded comparable, or somewhat better, protective effects but also caused clumping and detachment of cells when administrated alone.
Description
Biochemistry, 41, 8203-8211
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemistry
https://harc.rpi.edu/
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