Aβ1-42 enhances NMDA receptor sensitivity by activating the integrin signaling pathway

Field: Neuroscience (Life Sciences)

Event Abstract Back to Event Aβ1-42 enhances NMDA receptor sensitivity by activating the integrin signaling pathway Gabor Juhasz1, Gabriella Vass1, Zsolt Datki2, Akos Hunya1, Denes Budai3, Botond Penke1, 2 and Viktor Szegedi2* 1 Department of Medical Chemistry, University of Szeged, Hungary 2 Bay Zoltan Foundation of Applied Research, BAYGEN, Hungary 3 Department of Biology, University of Szeged, Hungary The accumulation and aggregation of a misfolded protein, Abeta1-42 is a central part of the pathomechanism of Alzheimer’s disease. Aggregated Abeta1-42 disrupts basic synaptic function and impairs synaptic plasticity by a yet largely unknown mechanism. Abeta1-42 has been shown to bind to several transmembrane proteins and activate numerous intracellular signal transduction pathways. Previously, we have repeatedly shown that aggregated Abeta1-42 increases NMDA evoked neuronal activity in vivo. In this study, we further characterized this phenomenon by investigating the role of integrin activation and downstream fyn kinase activity using in vivo single-unit recordings combined with microiontophoresis and in vitro Ca2+ influx measurements. Our results show that inhibiting Abeta1-42 and beta1 integrin interaction prevented the NMDA response enhancement and subsequent increased Ca2+ influx; however the control alpha2 antibody was not protective. Blocking fyn kinase activity with PP2 also prevented the effect of Abeta1-42 on NMDA receptors. In contrast, a control substance, PP3 had no effect on the Abeta1-42 induced overexcitation. These results support the hypothesis, that aggregated Abeta1-42 induces a fyn kinase dependent NMDA receptor phosphorylation by binding to the beta1 integrin subunit. These molecules may be novel targets for drug development against AD. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - degenerative disorders Citation: Juhasz G, Vass G, Datki Z, Hunya A, Budai D, Penke B and Szegedi V (2009). Aβ1-42 enhances NMDA receptor sensitivity by activating the integrin signaling pathway. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.157 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Mar 2009; Published Online: 05 Mar 2009. * Correspondence: Viktor Szegedi, Bay Zoltan Foundation of Applied Research, BAYGEN, Szeged, Hungary, szegediv@baygen.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gabor Juhasz Gabriella Vass Zsolt Datki Akos Hunya Denes Budai Botond Penke Viktor Szegedi Google Gabor Juhasz Gabriella Vass Zsolt Datki Akos Hunya Denes Budai Botond Penke Viktor Szegedi Google Scholar Gabor Juhasz Gabriella Vass Zsolt Datki Akos Hunya Denes Budai Botond Penke Viktor Szegedi PubMed Gabor Juhasz Gabriella Vass Zsolt Datki Akos Hunya Denes Budai Botond Penke Viktor Szegedi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.