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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/1843
Title: Interleukin-1beta interferes with signal transduction induced by neurotrophin-3 in cortical neurons.
Authors: Rungtip Soiampornkula
Tongb, Liqi
Wipawan Thangnipona
Balazsb, Robert
Cotmanb, Carl W.
Tongb, Liqi
Keywords: IL-1β;NT-3;signal transduction;cortical neurons;Open Access article
Issue Date: 2012
Citation: Brain Res. Vol.10, No.1188 (2008), 189-197
Abstract: It was previously observed that IL-1beta interferes with BDNF-induced TrkB-mediated signal transduction and protection of cortical neurons from apoptosis evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we investigated whether the effect of the cytokine on neurotrophin signaling is more general. The influence of IL-1beta on NT-3 signaling was therefore studied under conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk receptor autophosphorylation. IL-1beta reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. These are the steps that are also inhibited by IL-1beta in BDNF-induced signal transduction. The functional consequences of the effect of IL-1beta on NT-3 signaling were severe, as NT-3 protection of the trophic support-deprived cortical neurons was abrogated. In view of the role in the maintenance and plasticity of neurons of ERK, Akt and CREB, which are activated by neurotrophins, elevated IL-1beta levels in the brain in Alzheimer's disease and other neurodegenerative diseases might contribute to the decline in cognitive functions before the pathological signs of the disease develop.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/1843
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