Synthesis and investigations of -amyloid peptides and their fragments

B. Penke, M. Zarandi, J. Varga, O. Laskay, K. Soôs, K. Jost, L. Latzkovits

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Amyloid peptides had been found neurotoxic, however, recently these results have been discussed. Our aim was to synthesize and characterize unequivocally ihe human and rat [1-amyloid I -42 pepîides and some of their fragments and analogs. In the tlrsl experiments the following peptides were investigated: human and rat l 42, human 33-35, 32-35. 31-35, 30-35,21-35, 29-35,27-35, 26-35, and 25-35. Toxiciy of the amyloid peptides was investigated in vitro using cultures of ghal celts, prepared from 1 8-day-old embryonic rat ganglion cervicale superius. All the peptides proved to be toxic. The shortest toxic fragment was the 33-35 tripeptide. Amyloid peptides (even the short sequences) increase the intracellular Ca"' level in neurons and glial cells This effect could be measured with spectrofluoremetry. In another experiments, we have found that p-amyloid peptides do not interact with lachykinin receptors. The electrophysiological actions of -amyloid peptides and fragments are investigated on cat neocortical cells using an intracellular microelectrode to the surface of the intracellularly recorded cells. These in vivo experiments demonstrated that the elevated extracellular level of -amyloid peptides can rapidly induce direct changes in the firing activity and synaptic response of neocortical neurons The most remarkable changes were sustained elevation of firing, potentiation of the excitatory postsynaptic potential and large increase of postsynaptic Ca2 levels. These changes can contribute to Ca -dependent molecular events in the neurons and may lead eventually to excitotoxic cell death. Obviously, these experiments demonstrate very significant, fast and direct actions of the -amyloid peptides and short fragments without plaque formation. Some short peptides. e g. propionyl-IIe-lIe-Cly-LeuNH: inhibit the neuro-and gliatoxic effect of I 42. This potential antagonist serves as starting point for rational drug design.

Original languageEnglish
Pages (from-to)A972
JournalFASEB Journal
Issue number9
Publication statusPublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Penke, B., Zarandi, M., Varga, J., Laskay, O., Soôs, K., Jost, K., & Latzkovits, L. (1997). Synthesis and investigations of -amyloid peptides and their fragments. FASEB Journal, 11(9), A972.