@entity172 -induced cell signalling in a cellular model of XXXX .

@entity172 @entity9096 @entity5543 @entity53 @entity195 @entity35 @entity4113
@entity195 ( @entity195 ) is characterised by deposition of a 4 kDa amyloid-beta peptide (Abeta) into senile plaques of the affected brain. Abeta is a proteolytic product of the membrane protein, @entity5543 ( @entity5543 ). An alternative cleavage pathway involves alpha-secretase activity and results in secretion of a 100 kDa non-amyloidogenic @entity5543 (sAPPalpha) and therefore a potential reduction in Abeta secretion. We have shown that @entity172 induces alpha-cleavage and therefore results in the secretion of sAPPalpha. This secretion is signalled via MAP-kinase and PI-3 kinase signal-transduction pathways. These pathways also have the potential to inhibit the activation of @entity9096 (GSK), a protein involved in cell death. Therefore, the aim of this work was to further elucidate the @entity172 -mediated signaling pathways involved in @entity5543 processing, with particular emphasis on GSK activity. By stimulating @entity35 hypothalamic neuronal GT1-7 cells with @entity53 , we found that @entity172 decreases the activation state of GSK via the MAP kinase pathway. Moreover, the inhibition of GSK activity by @entity4113 causes enhanced sAPPalpha secretion in a pattern similar to that seen in response to @entity172 , suggesting a pivotal role for this deactivation in @entity5543 processing. Further, inactivation of GSK by @entity172 can be confirmed in an in vivo model. Elucidation of the signaling pathways involved in @entity5543 processing may help to understand the pathology of @entity195 and may also prove beneficial in developing therapeutic strategies to combat @entity195 .
