Neuroprotective Effects of New Protein Kinase C Activator TPPB Against A beta(25-35) Induced Neurotoxicity in PC12 Cells

作者：Yang, Hong-Qi^*; Li, Xue; Yang, Wei-Min; Feng, Shu-Man; Ma, Jian-Jun

来源：Neurochemical Research, 2012, 37(10): 2213-2221.

DOI：10.1007/s11064-012-0846-6

• Alzheimer's disease
• Protein kinase C
• beta-amyloid
• Neuroprotection

Alzheimer's disease (AD) is pathologically characterized by presence of senile plaques in the hippocampus, which are composed mainly of extracellular deposition of a polypeptide known as the beta amyloid, the A beta. It has been demonstrated on numerous occasions that it was the deposition and aggregation of this A beta peptide that cause neuronal dysfunction and even finally, the dementia. Lowering the deposition of A beta or decreasing its neurotoxicity has long been one of the purposes of AD therapy. In previous study, we reported that protein kinase C (PKC) activator TPPB could regulate APP processing by increasing alpha-secretase activity. In this study we further investigated the potential neuroprotective effect of TPPB against A beta(25-35)-induced neurotoxicity in PC12 cells. The results indicated that TPPB at concentration of 1 mu M could antagonize A beta(25-35) induced cell damage as evidenced by MTT assays, LDH release and by morphological changes. Furthermore, the neuroprotection in cell viability can be blocked by inhibitors of PKC, Akt and MAPK. The experiment also indicated that TPPB could increase the phosphorylation of Akt, PKC, MARCKS and MAPK, which were inhibited by A beta(25-35) treatment. Finally, TPPB inhibited the activation of caspase-3 induced by A beta(25-35). Taken together, the experiment here implies that TPPB has a role against A beta(25-35)-induced neurotoxicity in PC12 cells and may suggest its therapeutic potential in AD.

• 出版日期2012-10
• 单位河南省人民医院; 郑州大学