Apoptosis-mediated neurotoxicity induced by β-amyloid and PRP fragments

Gianluigi Forloni, Orso Bugiani, Fabrizio Tagliavini, Mario Salmona

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The neurotoxic activity of β-amyloid (βA) and prion protein (PrP) fragments contributed to the hypothesis concerning a causal role of amyloid deposits in Alzheimer disease (AD) and in prion-related encephalopathies. In this study, we investigated some aspects of the molecular mechanisms associated with neurotoxic activity of synthetic peptides homologous to βA (β 25-35) or PrP (PrP106-126) fragments. Chronic (5-7 d) exposure to both peptides induced neuronal death by apoptosis, as suggested by biochemical and morphological analysis. The apoptotic mechanism was confirmed by ultrastructural examination. The intracellular cascade of events activated by peptides was investigated by Northern blot and PCR analysis of expression of early genes (c-fos, c-jun, c-myc) and other proteins (p53, SGP-2bcl-2, HSP70, Ich-1) potentially involved in apoptosis. With the exception of bcl-2 mRNA decrease and a slight increase of SGP-2 in PrP106-126-treated cells, no consistent alterations of these mRNA expressions were found in neuronal cells exposed to β 25-35 or PrP106-126. Furthermore, we synthesized amidated homologs of both peptides with low amyloidogenic activity to test directly the relationship between amyloid fibrils and cell death. The neurotoxicity exhibited by PrP106-126-NH2 was similar to that observed with original peptide, whereas the amidation of β 25-35 partially reduced the neurotoxicity of this peptide.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalMolecular and Chemical Neuropathology
Issue number1-3
Publication statusPublished - May 1996


  • Alzheimer disease
  • amyloid
  • apoptosis
  • fibrils, gene expression
  • neurotoxicity
  • prion-related encephalopathies

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology


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