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Neurotoxic Effects of Aß6-42 Peptides Mimicking Putative Products Formed by the Angiotensin Converting Enzyme.
Medvedev, Alexei E; Radko, Sergey P; Yurinskaya, Marina M; Vinokurov, Maxim G; Buneeva, Olga A; Kopylov, Arthur T; Kozin, Sergey A; Mitkevich, Vladimir A; Makarov, Alexander A.
Afiliação
  • Medvedev AE; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Radko SP; Institute of Biomedical Chemistry, Moscow, Russia.
  • Yurinskaya MM; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Vinokurov MG; Institute of Biomedical Chemistry, Moscow, Russia.
  • Buneeva OA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Kopylov AT; Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
  • Kozin SA; Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
  • Mitkevich VA; Institute of Biomedical Chemistry, Moscow, Russia.
  • Makarov AA; Institute of Biomedical Chemistry, Moscow, Russia.
J Alzheimers Dis ; 66(1): 263-270, 2018.
Article em En | MEDLINE | ID: mdl-30282362
Angiotensin converting enzyme (ACE) is involved in proteolytic processing of the amyloid-ß(Aß) peptide implicated in the development of Alzheimer's disease (AD) and known products of ACE-based processing of Aß42 are characterized by reduced aggregability and cytotoxicity. Recently it has been demonstrated that ACE can act as an arginine specific endopeptidase cleaving the N-terminal pentapeptide (Aß1-5) from synthetic Aß peptide analogues. In the context of proteolytic processing of full length Aß42, this suggests possible formation of Aß6-42 species. The aim of this study was to test a hypothesis that some N-terminally truncated Aß peptide(s) could retain aggregability and neurotoxic properties typical for Aß42. We have investigated aggregability of two amyloid-ß peptides, Aß6-42 and isoD7-Aß6-42, mimicking potential proteolytic products of Aß42 and isoD7-Aß42, and evaluated their effects on the repertoire of brain Aß binding proteins, and cytotoxicity towards neuroblastoma SH-SY5Y cells. Aggregability of isoD7-Aß6-42 and Aß6-42 was higher than that of full-length peptides Aß42 and isoD7-Aß42, while the repertoire of mouse brain Aß binding proteins dramatically decreased. Aß6-42 and isoD7-Aß6-42 exhibited higher neurotoxicity towards SH-SY5Y cells than Aß42 and isoD7-Aß42, respectively. They effectively stimulated production of ROS and NO, and also TNFα secretion by cells. Thus, our results suggest that ACE-dependent processing of full-length Aßs could result in formation of more pathogenic peptides.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Peptidil Dipeptidase A / Materiais Biomiméticos Limite: Animals / Humans / Male Idioma: En Revista: J Alzheimers Dis Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Peptidil Dipeptidase A / Materiais Biomiméticos Limite: Animals / Humans / Male Idioma: En Revista: J Alzheimers Dis Ano de publicação: 2018 Tipo de documento: Article