Curcumin-induced degradation of PKCδ is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats

摘要: Polysialylation of the neural cell adhesion molecule (NCAM PSA) is necessary for consolidation processes hippocampus-based learning. Previously, we have found inhibition protein kinase C delta (PKCdelta) to be associated with increased polysialyltransferase (PST) activity, suggesting inhibitors this might ameliorate cognitive deficits. Using a rottlerin template, drug previously considered an inhibitor PKCdelta, searched Compounds Available Purchase (CAP) database Accelrys((R)) Catalyst programme structurally similar molecules and, using available crystal structure phorbol-binding domain that diferuloylmethane (curcumin) docked effectively into phorbol site. Curcumin NCAM PSA expression in cultured neuro-2A neuroblastoma cells and was inversely related PKCdelta expression. did not directly inhibit activity but formed tight complex enzyme. With increasing doses curcumin, Tyr(131) residue which known direct its degradation, became progressively phosphorylated numerous Tyr(131)-phospho-PKCdelta fragments. Chronic administration curcumin vivo also frequency polysialylated dentate infragranular zone significantly improved acquisition water maze spatial learning paradigm both adult aged cohorts Wistar rats. These results further confirm role regulating PST provide evidence modulation system enhances process memory consolidation.