| Summary: | 碩士 === 中國醫藥大學 === 醫學研究所碩士班 === 95 === Peroxisome proliferator-activated receptor alpha (PPARa) is a lipid- activated transcription factor playing important regulatory functions in development and metabolism. In this study, we determine the mechanism of PPARa activation on neuronal differentiation and degeneration. Using the model system of retinoic acid (RA)-induced differentiation of NT2/D1 cells into NT2N cells, NT2N cells have been demonstrated to express specific neuronal marker such as NeuroD, Mash1, Math1, and Nestin by RT-PCR, or protein expression of MAP2 and Cdk5 by Western blotting. Our results show that Wy14643 (PPARa agonist) accelerates neuronal differentiation by increasing the expression of NeuroD, Mash1, Math1, MAP2 and Cdk5. When compared with the RA group, addition of Wy14643 and RA increases ratio of GSK3b/p-GSK3b, and protein levels of b-catenin, p-ERK2, p-JNK and p-p38. In neuron degeneration, comet assay shows that activation of PPARa decreases the apoptotic proportion of NT2N cells treated with Ab42. When compared with the Ab42 group, addition of Wy14643 decreases protein levels of EndoG, AIF and GSK3b/p-GSK3b ratio, and inhibits EndoG translocates from cytoplasm into nucleus. We conclude that the activation of PPARa accelerates neuronal differentiation by a mechanism that may involve a cross talk between Wnt signaling pathway and MAP kinase pathway. Additionally, activation of PPARa attenuates Ab-dependent neurodegeneration by decreasing protein expression of EndoG and AIF.
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