Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide

Autor: Marie-Pierre Dehouck, Howard Fillit, Fenart Laurence, Andrew Scanameo, Beatrice Leveugle, Roméo Cecchelli, Wanhong Ding
Přispěvatelé: Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA)
Rok vydání: 1998
Předmět:
Models
Neurological
Oligosaccharides
Peptide
Heparan sulfate
Biology
Blood–brain barrier
Biochemistry
Glycosaminoglycan
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Amyloid beta-Protein Precursor
0302 clinical medicine
medicine
Amyloid precursor protein
Animals
Secretion
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
Glycosaminoglycans
chemistry.chemical_classification
0303 health sciences
Heparin
food and beverages
Alzheimer's disease
Heparin
Low-Molecular-Weight
In vitro
Coculture Techniques
3. Good health
Capillaries
Rats
Kinetics
medicine.anatomical_structure
chemistry
Blood-Brain Barrier
Astrocytes
Cerebrovascular Circulation
biology.protein
Proteoglycans
Therapy
Endothelium
Vascular
030217 neurology & neurosurgery
medicine.drug
Zdroj: Journal of Neurochemistry
Journal of Neurochemistry, Wiley, 1998, 70 (2), p. 736-744
ISSN: 0022-3042
1471-4159
Popis: International audience; We have previously demonstrated that full-length heparin stimulates the synthesis and secretion of β-amyloidprecursor protein (APP) through an amyloidogenic pathway in neuroblastoma cells. In the present study, heparin was chemically depolymerized, and the effect of low-molecular-weight (LMW) hepanin on APP secretion was investigated. In contrast to full-length hepar, LMW heparin had no significant effect on APP secretion. However, LMW heparin fragments, especially heparin disaccharides, were able to inhibit efficiently the stimulatory effect of heparin on APP secretion. LMW heparin derivatives also inhibit the binding of heparin to the β-amyloid peptide (1-28). Using an in vitro model, we further demonstrated the passage of LMW heparin derivatives through the blood-brain barrier. This study suggests that LMW heparin derivatives or analogues may be effective as therapeutic agents to prevent or slow the process of amyloidogenesis in Alzheimer's disease.
Databáze: OpenAIRE
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