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- Cheng, FangLund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups (författare)
Non-toxic amyloid beta formed in the presence of glypican-1 or its deaminatively generated heparan sulfate degradation products
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
- 2013-09-10
- Oxford University Press (OUP),2013
Nummerbeteckningar
- LIBRIS-ID:oai:lup.lub.lu.se:be8009e7-f4ab-4e68-ac65-0c991e4fa656
- https://lup.lub.lu.se/record/4196541URI
- https://doi.org/10.1093/glycob/cwt079DOI
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- Språk:engelska
- Sammanfattning på:engelska
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Anmärkningar
- The amyloid beta (A beta) peptides (mainly A beta 40 and A beta 42), which are derived from the amyloid precursor protein (APP), can oligomerize into antibody A11-positive, neurotoxic species, believed to be involved in Alzheimer's disease. Interestingly, APP binds strongly to the heparan sulfate (HS) proteoglycan (PG) glypican-1 (Gpc-1) in vitro and both proteins are colocalized inside cells. In endosomes, APP is proteolytically processed to yield A beta peptides. The HS chains of S-nitrosylated (SNO) Gpc-1 PG are cleaved into anhydromannose (anMan)-containing di- and oligosaccharides by an NO-dependent reaction in the same compartments. Here, we have studied the toxicity of oligomers/aggregates of A beta 40 and A beta 42, as well as A beta 40/42 mixtures that were formed in the presence of immobilized Gpc-1 PG or immobilized HS oligosaccharides. Afterwards, A beta was displaced from the matrices, analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and assayed for A11 immunoreactivity, for effects on growth of mouse N2a neuroblastoma cells and for membrane leakage in rat cortical neurons. HS generally promoted and accelerated A beta multimerization into oligomers as well as larger aggregates that were mostly A11 positive and showed toxic effects. However, non-toxic A beta was formed in the presence of Gpc-1 PG or when anMan-containing HS degradation products were simultaneously generated. Both toxic and non-toxic A beta peptides were taken up by the cells but toxic forms appeared to enter the nuclei to a larger extent. The protection afforded by the presence of HS degradation products may reflect a normal intracellular function for the A beta peptides.
Ämnesord och genrebeteckningar
- NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
- NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
- amyloid beta
- glypican-1
- heparan sulfate
- oligomerization
- toxicity
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Ruscher, KarstenLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-ktr (författare)
- Fransson, Lars-ÅkeLund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups(Swepub:lu)medk-laf (författare)
- Mani, KatrinLund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups(Swepub:lu)medk-kma (författare)
- GlykobiologigruppenForskargrupper vid Lunds universitet (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Glycobiology: Oxford University Press (OUP)23:12, s. 1510-15191460-24230959-6658
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