Nicotinamide mononucleotide improves energy activity and survival rate in an in vitro model of Parkinson's disease

Lu,Lei; Tang,Le; Wei,Wenshi; Hong,Yunyi; Chen,Heyu; Ying,Weihai; Chen,Shengdi

doi:10.3892/etm.2014.1842

Nicotinamide mononucleotide improves energy activity and survival rate in an in vitro model of Parkinson's disease

Authors:
- Lei Lu
- Le Tang
- Wenshi Wei
- Yunyi Hong
- Heyu Chen
- Weihai Ying
- Shengdi Chen
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Affiliations: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Neurology, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China, School of Biomedical Engineering and Med‑X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Department of Neurology and Institute of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
Published online on: July 14, 2014 https://doi.org/10.3892/etm.2014.1842
Pages: 943-950

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Abstract

Nicotinamide adenine dinucleotide (NAD+) repletion has been shown to provide marked neuroprotection from genotoxic agent‑induced neuronal and astrocyte cell death. One of the key precursors of NAD+ is nicotinamide mononucleotide (NMN). Therefore, it was hypothesized that NMN may attenuate apoptosis and improve energy metabolism in Parkinson's disease (PD)‑like behavioral and neuropathological changes, and produce significant beneficial effects. In this study, a cellular model of PD, using rotenone‑treated PC12 cells, was established to test the hypothesis that NMN may decrease PD‑like pathological changes. Experiments were carried out to investigate cell survival, including an intracellular lactate dehydrogenase (LDH) assay. Apoptotic and necrotic cell death, NAD+ levels and ATP levels were also evaluated. It was observed that NMN was able to significantly attenuate the rotenone‑induced reduction in the survival rate of PC12 cells, as assessed by MTT and LDH assays. NMN treatment also significantly reduced the rotenone‑induced apoptosis of the cells, as assessed by flow cytometry‑based Annexin V/7‑aminoactinomycin D staining. Furthermore, NMN restored intracellular levels of NAD+ and ATP in the rotenone‑treated cells, thus demonstrating the capacity of NMN to ameliorate mitochondrial inhibitor‑induced impairments of energy metabolism. The present study indicates that NMN produces significant beneficial effects by attenuating apoptosis and improving energy metabolism in a cellular model of PD. These results suggest that NMN may become a promising therapeutic drug for PD.

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