Beta-amyloid-derived pentapeptide RIIGLa inhibits Abeta(1-42) aggregation and toxicity.

Abstract

Pr-IIGL(a), a derivative of the tetrapeptide beta-amyloid 31-34 (Abeta(31-34)), exerts controversial effects: it is toxic in a neuroblastoma culture, but it protects glial cells from the cytotoxic action of Abeta(1-42). For an understanding of this phenomenon, a new pentapeptide, RIIGL(a) was synthetized, and both compounds were studied by different physicochemical and biological methods. Transmission electron microscopic (TEM) studies revealed that Pr-IIGL(a) forms fibrillar aggregates, whereas RIIGL(a) does not form fibrils. Congo red binding studies furnished the same results. Aggregated Pr-IIGL(a) acts as a cytotoxic agent in neuroblastoma cultures, but RIIGL(a) does not display inherent toxicity. RIIGL(a) co-incubated with Abeta(1-42) inhibits the formation of mature amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar Abeta(1-42). These results indicate that RIIGL(a) is an effective inhibitor of both the aggregation and the toxic effects of Abeta(1-42) and can serve as a lead compound for the design of novel neuroprotective peptidomimetics.

• Authors: Lívia Fülöp, Márta Zarándi, Zsolt Datki, Katalin Soós, Botond Penke
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 324 Issue 1 Pg. 64-9 (Nov 05 2004) ISSN: 0006-291X [Print] United States
• PMID: 15464983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Coloring Agents
• Oligopeptides
• Peptide Fragments
• amyloid beta-protein (1-42)
• propionyl-isoleucyl-isoleucyl-glycyl-leucinamide
• Congo Red

Topics

• Amyloid beta-Peptides (antagonists & inhibitors, metabolism, toxicity, ultrastructure)
• Cell Differentiation
• Cell Line, Tumor
• Cell Survival
• Coloring Agents (metabolism)
• Congo Red (metabolism)
• Humans
• Neuroblastoma (metabolism, pathology)
• Oligopeptides (chemistry, genetics, metabolism, pharmacology)
• Peptide Fragments (chemistry, genetics, metabolism, pharmacology, toxicity)