Beta-amyloid-derived pentapeptide RIIGLa inhibits Abeta(1-42) aggregation and toxicity.
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.
Fülöp
Lívia
L
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary. fulopl@index.hu <fulopl@index.hu>
Zarándi
Márta
M
Datki
Zsolt
Z
Soós
Katalin
K
Penke
Botond
B
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity* / Q000648:ultrastructure; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D004396:Coloring Agents / Q000378:metabolism; D003224:Congo Red / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D009842:Oligopeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C106796:propionyl-isoleucyl-isoleucyl-glycyl-leucinamide; D003224:Congo Red