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

Luigi Bergamaschini, Cesare Donarini, Emanuela Rossi, Ada De Luigi, Carlo Vergani, Maria Grazia De Simoni

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)531-536
Number of pages6
JournalNeurobiology of Aging
Volume23
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

Amyloid
Heparin
Aptitude
High Molecular Weight Kininogens
Serum Amyloid A Protein
PC12 Cells
In Vitro Techniques
Alzheimer Disease
Inflammation
Amino Acids
Pharmaceutical Preparations

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • C4
  • Complement
  • Contact system
  • Heparin
  • High molecular weight kininogen
  • Inflammation
  • Neurotoxicity
  • PC12

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-β in vitro. / Bergamaschini, Luigi; Donarini, Cesare; Rossi, Emanuela; De Luigi, Ada; Vergani, Carlo; Grazia De Simoni, Maria.

In: Neurobiology of Aging, Vol. 23, No. 4, 2002, p. 531-536.

Research output: Contribution to journalArticle

Bergamaschini, Luigi ; Donarini, Cesare ; Rossi, Emanuela ; De Luigi, Ada ; Vergani, Carlo ; Grazia De Simoni, Maria. / Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-β in vitro. In: Neurobiology of Aging. 2002 ; Vol. 23, No. 4. pp. 531-536.
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