Protective effect of caffeic acid against beta-amyloid-induced neurotoxicity by the inhibition of calcium influx and tau phosphorylation.
OBJECTIVE
The progressive accumulation of beta-amyloid peptide (Abeta), in the form of senile plaques, has been recognized as one of the major causes of Alzheimer's disease (AD) pathology. Increased production of Abeta and the aggregation of Abeta to oligomers have been reported to trigger neurotoxicity, oxidative damage and inflammation. Furthermore, Abeta-induced tau hyperphosphorylation and neurotoxicity are downstream of Abeta. Therefore, we studied the possible neuroprotective effects of caffeic acid against Abeta-induced toxicity.


METHODS
Treatment of PC12 cells with 10 microM Abeta (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-3beta (glycogen synthase kinase-3beta) activation (phosphorylation).


RESULTS
However, pretreatment of the PC12 cells with 10 and 20 microg/ml of caffeic acid, for 1 h prior to Abeta, significantly reversed the Abeta-induced neurotoxicity by attenuating the elevation of intracellular calcium levels and tau phosphorylation.


CONCLUSIONS
Taken together, these results suggest that caffeic acid protected the PC12 cells against Abeta-induced toxicity. In addition, the neuroprotective mechanisms of caffeic acid against Abeta attenuated intracellular calcium influx and decreased tau phosphorylation by the reduction of GSK-3beta activation.
Sul
Donggeun
D
Environmental Toxico-Genomic and Proteomic Center, College of Medicine, Korea University, Anamdong 5, Sungbuk-Ku, Seoul 136-701, Republic of Korea.
Kim
Hyo-Shin
HS
Lee
Dongho
D
Joo
Seong Soo
SS
Hwang
Kwang Woo
KW
Park
So-Young
SY
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002109:Caffeic Acids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002109:Caffeic Acids; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D002118:Calcium; C040048:caffeic acid