α-Synuclein Inhibits the Expression of BDNF in PC12 Cells

Abstract

Abstract: Objective：To research the effect of α-synuclein on the brain derived neurophic factor (BDNF) expression. Methods：Recombinant plasmids were constructed using molecular techniques and were used to transfect mammalian cells. The protein level was examined by western blotting assay and the activity of transcription factors was tested by dual-luciferase reporter assay system. Results：Overexpression of α-synuclein inhibited the expression of BDNF and attenuated the transcription activity of cAMP response element binding protein (CREB)，but did not affect the activity of Nurr1. Besides，CREB ser-133 phosphorylation level was decreased when α-synuclein was overexpressed. Conclusion：Overexpressed α-synuclein down-regulates BDNF probably through depressing the activities of CREB transcription factors.

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Key words: alpha, -synuclein, brain derived neurophic factor（BDNF）, transcription factor, transactivity

CLC Number:

YUAN Yu-he，WU Miao-miao，HU Jin-feng，CHEN Nai-hong. α-Synuclein Inhibits the Expression of BDNF in PC12 Cells[J]. Acta Neuropharmacologica, 2011, 1(4): 1-5.

References

1.      Thomas B, Beal MF. Parkinson's disease[J]. Hum Mol Genet, 2007, 16(02): R183-194.
2.      Min Jeong Park, Sang-Myung Cheon, Hye-Ran Bae, et al.Elevated levels of α-synuclein oligomer in the cerebrospinal fluid of drug-naïve patients with Parkinson's disease[J].J Clin Neurol, 2011, 7(4):215-222.
3.      Gizem Donmez, Anirudh Arun, Chee-Yeun Chung, et al. SIRT1 protects against α-synuclein aggregation by activating molecular chaperones[J]. J Neurosci, 2012, 32(1):124-132.
4.      Charalambos Karakasis, Kallirhoe Kalinderi, Zoe Katsarou, et al. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with Parkinson's disease in a Greek population[J]. J Clin Neurosci, 2011, 18(12):1744-1745.
5.      Tofaris GK, Spillantini MG. Alpha-synuclein dysfunctionin lewy body diseases[J]. Mov Disorders, 2005, 20(Suppl 12): S37-44.
6.      Beyer Katrin, Ariza Aurelio. Protein aggregation mechanisms in synucleinopathies: commonalities and differences[J]. J Neuropathol Exp Neurol, 2007, 66(11): 965-974.
7.      George J Siegel, Neelima B Chauhan. Neurotrophic factors in Alzheimer's and Parkinson's disease brain[J]. Brain Res Brain Res Rev, 2000, 33(2-3): 199-227.
8.      Changgeng Peng, Liviu Aron, Rudiger Klein, et al. Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons[J]. J Neurosci, 2011, 31(36):12802-12815.
9.      Tamara Aid, Anna Kazantseva, Marko Piirsoo, et al. Mouse and rat BDNF gene structure and expression revisited[J]. J Neurosci Res, 2007, 85(3): 525-535.
10. Yuan Y[J]. Cell Mol Neurobiol, 2008, 28(1): 21-33.uhe, Jin Jin, Yang Bo, et al. Overexpressed alpha-synuclein regulated the nuclear factor-kappaB signal pathway
11. Chinta SJ, AndersenJK. Dopaminergic neurons[J]. Int J Biochem Cell Biol, 2005, 37(5): 942-946.
12. Le Weidong, Pan Tianhong, Huang Maosheng, et al. Decreased NURR1 gene expression in patients with Parkinson's disease[J]. J Neurol Sci, 2008, 273(1-2): 29-33.
13. Lee B, Cao R, Choi YS, et al. The CREB/CRE transcriptional pathway: protection against oxidative stress-mediated neuronal cell death[J]. J Neurochem, 2009, 108(5): 1251-1265.

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