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.
TGF-beta1 protects against A beta-neurotoxicity via the phosphatidylinositol-3-kinase pathway / Caraci, F; Battaglia, G; Busceti, C; Biagioni, F; Mastroiacovo, F; Bosco, P; Drago, F; Nicoletti, Ferdinando; Sortino, Ma; Copani, A.. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 30:(2008), pp. 234-242. [10.1016/j.nbd.2008.01.007]
TGF-beta1 protects against A beta-neurotoxicity via the phosphatidylinositol-3-kinase pathway.
BATTAGLIA G;NICOLETTI, Ferdinando;
2008
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
