| Literature DB >> 18356065 |
Filippo Caraci1, Giuseppe Battaglia, Carla Busceti, Francesca Biagioni, Federica Mastroiacovo, Paolo Bosco, Filippo Drago, Ferdinando Nicoletti, Maria Angela Sortino, Agata Copani.
Abstract
beta-Amyloid (A beta) injection into the rat dorsal hippocampus had a small neurotoxic effect that was amplified by i.c.v. injection of SB431542, a selective inhibitor of transforming growth factor-beta (TGF-beta) receptor. This suggested that TGF-beta acts as a factor limiting A beta toxicity. We examined the neuroprotective activity of TGF-beta1 in pure cultures of rat cortical neurons challenged with A beta. Neuronal death triggered by A beta is known to proceed along an aberrant re-activation of the cell cycle, and involves late beta-catenin degradation and tau hyperphosphorylation. TGF-beta1 was equally protective when added either in combination with, or 6 h after A beta. Co-added TGF-beta1 prevented A beta-induced cell cycle reactivation, whereas lately added TGF-beta1 had no effect on the cell cycle, but rescued the late beta-catenin degradation and tau hyperphosphorylation. The phosphatidylinositol-3-kinase (PI-3-K) inhibitor, LY294402, abrogated all effects. Thus, TGF-beta1 blocks the whole cascade of events leading to A beta neurotoxicity by activating the PI-3-K pathway.Entities:
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Year: 2008 PMID： 18356065 DOI： 10.1016/j.nbd.2008.01.007
Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996