Potent anti-angiogenic motifs within the Alzheimer beta-amyloid peptide.

Abstract

Abeta peptides are the major constituents of senile plaques and cerebrovascular deposits in the brains of patients with Alzheimer's disease. We have shown previously that Abeta1-40 and Abeta1-42 peptides are potently anti-angiogenic both in vitro and in vivo. The current study characterizes important sequences within the Abeta peptide that are required to exert its anti-angiogenic activity. We have used human umbilical vein endothelial cells to assess the anti-angiogenic activity of short fragments of Abetain vitro in a Matrigel network assay and in vivo in a rat corneal model of angiogenesis. The anti-angiogenic activity of these short peptide fragments is not related to effects on apoptosis or necrosis. Using normal and mutated peptide fragments, we show that the sequence VHHQKLVFF is sufficient to exhibit potent anti-angiogenic effects. This small peptide may therefore have clinical relevance as an anti-angiogenic agent.

• Authors: Nikunj S Patel, Amita Quadros, Steven Brem, Marguerite Wotoczek-Obadia, Venkatarajan S Mathura, Vincent Laporte, Michael Mullan, Daniel Paris
• Journal: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis (Amyloid) Vol. 15 Issue 1 Pg. 5-19 (Mar 2008) ISSN: 1350-6129 [Print] England
• PMID: 18266117 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amyloid beta-Peptides
• Angiogenesis Inhibitors
• Oligopeptides
• Peptide Fragments
• amyloid beta-protein (1-40)

Topics

• Alzheimer Disease (genetics, metabolism, pathology)
• Amino Acid Motifs (genetics)
• Amyloid beta-Peptides (genetics, metabolism, pharmacology)
• Angiogenesis Inhibitors (genetics, metabolism, pharmacology)
• Animals
• Brain
• Cells, Cultured
• Corneal Neovascularization (chemically induced, genetics, metabolism, pathology)
• Endothelial Cells (metabolism, pathology)
• Humans
• Mutation
• Oligopeptides (metabolism, pharmacology)
• Peptide Fragments (genetics, metabolism, pharmacology)
• Rats
• Umbilical Veins (metabolism, pathology)