Protective effect of caffeic acid against beta-amyloid-induced neurotoxicity by the inhibition of calcium influx and tau phosphorylation

Abstract

Aims: The progressive accumulation of beta-amyloid peptide (A beta), in the form of senile plaques, has been recognized as one of the major causes of Alzheimer's disease (AD) pathology. Increased production of A beta and the aggregation of A beta, to oligomers have been reported to trigger neurotoxicity, oxidative damage and inflammation. Furthermore, A beta-induced tau hyperphosphorylation and neurotoxicity are downstream of A beta. Therefore, we studied the possible neuroprotective effects of caffeic acid against A beta-induced toxicity. Main methods: Treatment of PC12 cells with 10 mu M A beta (25-35) for 24 h significantly decreased the cell viability; this was accompanied by an increase in intracellular calcium levels and tau phosphorylation with GSK-3 beta (glycogen synthase kinase-3 beta) activation (phosphorylation). Key findings: However, pretreatment of the PC12 cells with 10 and 20 mu g/ml of caffeic acid. for 1 h prior to A beta, significantly reversed the A beta-induced neurotoxicity by attenuating the elevation of intracellular calcium levels and tau phosphorylation. Significance: Taken together, these results suggest that caffeic acid protected the PC12 cells against A beta-induced toxicity. In addition, the neuroprotective mechanisms of caffeic acid against A beta attenuated intracellular calcium influx and decreased tau phosphorylation by the reduction of GSK-3 beta activation. (C) 2008 Elsevier Inc. All rights reserved.