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.