Nicotinamide mononucleotide adenylyltransferase 1 ameliorates dopaminergic neuron death via attenuating apoptosis and oxidation in MPTP-treated mice

作者：Hou, Wen-Long; Liang, Dong; Niu, Meng-Yue; Wang, Jing; Zhou, Chang; Xie, An-Mu^*

来源：International Journal of Clinical and Experimental Medicine, 2018, 11(6): 5722-5728.

• NMNAT1
• axonal degeneration
• Parkinson's disease

Background: Axonal degeneration is a primary or contributing component of Parkinson's disease (PD). Studies have found that the full sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is the chief component of Wallerian degeneration slow (WldS) protein, which could delay axonal degeneration. In addition, Nmnat1 is required and sufficient for the protective effects of WldS. However, the role of NMNAT1 in PD has not been clearly established. Methods: In the present study, we established a PD model using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were divided into the following groups: vehicle group, MPTP-treated vehicle group and MPTP-treated NMNAT1-overexpression group. We evaluated motor coordination ability with the rotarod test. The nigrostriatal pathway was tested by TH immunofluorescence staining and catecholamine measurements. In addition, we assessed the possible molecular mechanisms of NMNAT1-mediated neuroprotection via Western blot analysis in the PD model. Results: We found that overexpression of NMNAT1 significantly improved motor coordination ability in MPTP-treated mice. Further studies showed that NMNAT1 could attenuate dopaminergic neural death and increase striatal levels of DA as well as the metabolites DOPAC and HVA in MPTP-treated mice. In addition, we found that overexpression of NMNAT1 abrogated the MPTP-induced decrease in the Bcl-2/Bax ratio and SOD1 expression. Conclusions: Our study demonstrated that overexpression of NMNAT1 could improve motor coordination ability and ameliorate degeneration of the nigrostriatal pathway in MPTP-treated mice. The mechanisms of this NMNAT1-mediated effect might rely on the inhibition of apoptosis and oxidation. Together, these findings reveal novel roles for NMNAT1 in PD and provide new therapeutic avenues for the treatment of the disease.

• 出版日期2018
• 单位青岛大学