Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-β in vitro

• Published in: Neurobiology of aging 2002-07, Vol.23 (4), p.531-536
• Main Authors: Bergamaschini, Luigi, Donarini, Cesare, Rossi, Emanuela, De Luigi, Ada, Vergani, Carlo, Grazia De Simoni, Maria
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - isolation & purification; Amyloid beta-Peptides - toxicity; Amyloid-β; Animals; Anticoagulants - pharmacology; Biological and medical sciences; Blotting, Western; Cell Survival - drug effects; Cells, Cultured; Complement; Complement Activation - drug effects; Contact system; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Densitometry; Heparin; Heparin - pharmacology; High molecular weight kininogen; Humans; Indicators and Reagents; Inflammation; Inflammation - chemically induced; Inflammation - prevention & control; Medical sciences; Neurology; Neurons - drug effects; Neurotoxicity; PC12; PC12 Cells; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - isolation & purification; Peptide Fragments - toxicity; Rats
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(02)00003-9

Amyloid-β protein (Aβ) is implicated in the pathogenesis of Alzheimer’s disease because of its neurotoxicity and the ability to trigger local inflammation. Compounds that interact with the amino acids of the N-terminal region or interfere with aggregation can reduce the Aβ biologic activity. We evaluated the effect of heparin on Aβ (1–42) neurotoxicity and on its ability to activate complement and contact system. On differentiated PC12 cells, a reliable model of neuronal cells, heparin at the doses of 10 and 20 μg/ml significantly counteracted Aβ cytotoxicity as assessed by measuring MTT conversion. We then explored the effect of heparin on Aβ (1–42)-induced complement and contact system activation. Aβ (1–42) was incubated with heparin in presence of normal plasma as the source of complement and contact system factors. Heparin reduced, in a dose-dependent manner, complement and contact system activation, assessed by measuring the degree of C4 and high molecular weight kininogen cleavage. The present data show that heparin can attenuate neurotoxic and pro-inflammatory activity of Aβ and suggest that this drug could represent a new strategy to reduce the progressive neurodegeneration in AD.