Influence of mutations associated with familial prion-related encephalopathies on biological activity of prion protein peptides

G. Forloni, N. Angeretti, P. Malesani, E. Peressini, T. Rodriguez Martin, P. Della Torre, Mario Salmona

Research output: Contribution to journalArticlepeer-review

Abstract

In transmissible spongiform encephalopathies (TSEs), an altered form of prion protein (PrP), PrPres, aggregates in amyloid fibrils and accumulates in the brain. Several point mutations of the PrP gene have been associated with the TSEs, so, to investigate how the mutations affect the biological activity of PrP, we analyzed the biological effects and chemicophysical characteristics of the peptide homologous to the wild-type and mutated sequence of PrP fragments. The mutation P102L altered the biological activity of PrP 89-106, which became neurotoxic without changing its fibrillogenic capacity. The mutation (D178N) in the PrP 169-185 strongly increased the neurotoxic activity of the native sequence. In this case, there was also a clear alteration of the structural conformation. None of the other mutations considered, including A117V, seemed to influence the biological activities of the respective peptides. These data identify new neurotoxic fragments of PrP in the mutated form and elucidate their genetic influence on the pathogenesis of TSEs.

Original languageEnglish
Pages (from-to)489-494
Number of pages6
JournalAnnals of Neurology
Volume45
Issue number4
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Neuroscience(all)

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