alpha-Synuclein expression is induced by depolarization and cyclic AMP in enteric neurons

作者：Paillusson Sebastien; Tasselli Maddalena; Lebouvier Thibaud; Mahe Maxime Michael; Chevalier Julien; Biraud Mandy; Cario Toumaniantz Chystelle; Neunlist Michel; Derkinderen Pascal^*

来源：Journal of Neurochemistry, 2010, 115(3): 694-706.

DOI：10.1111/j.1471-4159.2010.06962.x

• alpha-synuclein
• cyclic AMP
• depolarization
• enteric nervous system
• extracellular signal-regulated kinases
• Parkinson's disease

P>Accumulated evidence emphasizes the importance of alpha-synuclein expression levels in Parkinson's disease (PD) pathogenesis. PD is a multicentric disorder that affects the enteric nervous system (ENS), whose involvement may herald the degenerative process in the CNS. We therefore undertook the present study to investigate the mechanisms involved in the regulation of expression of alpha-synuclein in the ENS. The regulation of alpha-synuclein expression was assessed by qPCR and western blot analysis in rat primary culture of ENS treated with KCl and forskolin. A pharmacological approach was used to decipher the signaling pathways involved. Intraperitoneal injections of Bay K-8644 and forskolin were performed in mice, whose proximal colons were further analyzed for alpha-synuclein expression. Depolarization and forskolin increased alpha-synuclein mRNA and protein expression in primary cultures of ENS, although L-type calcium channel and protein kinase A, respectively. Both stimuli increased alpha-synuclein expression through a Ras/extracellular signal-regulated kinases pathway. An increase in alpha-synuclein expression was also observed in vivo in the ENS of mice injected with Bay K-8644 or forskolin. In conclusion, we have identified stimuli leading to alpha-synuclein over-expression in the ENS, which could be critical in the initiation of the pathological process in PD.

• 出版日期2010-11