Related Experiment Video
Updated: Jun 17, 2026
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Heparan sulfate mediates amyloid-beta internalization and cytotoxicity
Elina Sandwall1, Paul O'Callaghan, Xiao Zhang
1Department of Medical Biochemistry and Microbiology, University of Uppsala, The Biomedical Center, Box 582, SE-751 23, Uppsala, Sweden.
Glycobiology
|January 8, 2010
Summary
Cell-surface heparan sulfate (HS) mediates the internalization and toxicity of amyloid-beta (Abeta) in Alzheimer's disease models. HS-deficient cells resist Abeta toxicity, indicating HS is crucial for Abeta uptake and damage.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Heparan sulfate (HS) is found with amyloid deposits in Alzheimer's disease (AD) brains.
- The role of HS in amyloid-beta (Abeta) pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the function of HS in Abeta internalization and toxicity using cell models.
Main Methods:
- Utilized wild-type (CHO-WT) and HS-deficient (pgsD-677) Chinese hamster ovary cells.
- Employed immunocytochemistry to assess Abeta internalization.
- Examined Abeta toxicity in cells with altered heparanase expression and in endothelial cells treated with heparin.
Main Results:
- HS-deficient cells showed resistance to Abeta40 toxicity compared to wild-type cells.
- Abeta internalization was observed in wild-type cells but not in HS-deficient cells.
- Heparanase overexpression and heparin treatment attenuated Abeta toxicity and internalization.
Conclusions:
- Cell-surface heparan sulfate plays a critical role in mediating Abeta internalization.
- HS is a key factor in Abeta-induced cellular toxicity, suggesting it as a potential therapeutic target in Alzheimer's disease.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...