Fibrillar Aβ1-42enhances NMDA receptor sensitivity via the integrin signaling pathway

Gábor Juhász, Balázs Barkóczi, Gabriella Vass, Zsolt Datki, Ákos Hunya, Lívia Fülöp, Dénes Budai, Botond Penke, Viktor Szegedi

Research output: Article

13 Citations (Scopus)


The aggregated form of amyloid-β (Aβ)1-42has been shown to increase N-methyl-D-aspartic acid (NMDA) evoked neuronal activity in vivo. Here we further characterized this phenomenon by investigating the role of integrin activation and downstream Src kinase activity using in vivo electrophysiology and in vitro intracellular Ca2+measurements. Pretreatment of differentiated SH-SY5Y cells with fibrillar Aβ1-42markedly enhanced the intracellular calcium increases caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against β1 integrin depressed the facilitatory effects of Aβ1-42. Similarly, Aβ1-42facilitated NMDA-R driven firing of hippocampal neurons in vivo, and this effect was reduced by neutralizing antibody against β1 integrins. The positive action of Aβ1-42on NMDA-R dependent responses was also depressed by an inhibitor known to block Src kinase. These results support the hypothesis that aggregated Aβ1-42is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.

Original languageEnglish
Pages (from-to)1055-1067
Number of pages13
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - jan. 1 2010


ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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