β-Amyloid-derived pentapeptide RIIGL a inhibits Aβ 1–42 aggregation and toxicity

Abstract

Pr-IIGL a, a derivative of the tetrapeptide β-amyloid 31–34 (Aβ 31–34), exerts controversial effects: it is toxic in a neuroblastoma culture, but it protects glial cells from the cytotoxic action of Aβ 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 Aβ 1–42 inhibits the formation of mature amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar Aβ 1–42. These results indicate that RIIGL a is an effective inhibitor of both the aggregation and the toxic effects of Aβ 1–42 and can serve as a lead compound for the design of novel neuroprotective peptidomimetics.