Potent anti-angiogenic motifs within the Alzheimer beta-amyloid peptide.
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.
Patel
Nikunj S
NS
The Roskamp Institute, Sarasota, Florida 34243, USA. npatel@rfdn.org
Quadros
Amita
A
Brem
Steven
S
Wotoczek-Obadia
Marguerite
M
Mathura
Venkatarajan S
VS
Laporte
Vincent
V
Mullan
Michael
M
Paris
Daniel
D
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020816:Amino Acid Motifs / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain; D002478:Cells, Cultured; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D014471:Umbilical Veins / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides; D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)