β-Amyloid-derived pentapeptide RIIGLa inhibits Aβ1–42 aggregation and toxicity

• DOI: 10.1016/j.bbrc.2004.09.024
• Publication Date: 2004-09-24T21:01:27Z
• Authors: Lívia Fülöp; Márta Zarándi; Zsolt Datki; Katalin Soós; Botond Penke
• Keywords: Pentapeptide repeat; Tetrapeptide; Amyloid (mycology); Peptidomimetic

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.