ABSTRACT
Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme that mediates various redox reactions. Particularly, mitochondrial NAD plays a critical role in energy production pathways, including the tricarboxylic acid (TCA) cycle, fatty acid oxidation, and oxidative phosphorylation. NAD also serves as a substrate for ADP-ribosylation and deacetylation by poly(ADP-ribose) polymerases (PARPs) and sirtuins, respectively. Thus, NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response. Numerous studies have demonstrated the involvement of NAD metabolism in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and retinal degenerative diseases. Mitochondrial dysfunction is considered crucial pathogenesis for neurodegenerative diseases such as AD and PD. Maintaining appropriate NAD levels is important for mitochondrial function. Indeed, decreased NAD levels are observed in AD and PD, and supplementation of NAD precursors ameliorates disease phenotypes by activating mitochondrial functions. NAD metabolism also plays an important role in axonal degeneration, a characteristic feature of peripheral neuropathy and neurodegenerative diseases. In addition, dysregulated NAD metabolism is implicated in retinal degenerative diseases such as glaucoma and Leber congenital amaurosis, and NAD metabolism is considered a therapeutic target for these diseases. In this review, we summarize the involvement of NAD metabolism in axon degeneration and various neurodegenerative diseases and discuss perspectives of nutritional intervention using NAD precursors.
Acknowledgments
K.H., K.O., K.Y., and T.N. wrote the manuscript. T.N. and K.H. revised and edited the manuscript. All authors approved the final version of the manuscript.
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No potential conflict of interest was reported by the authors.
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Notes on contributors
Keisuke Hikosaka
Keisuke Hikosaka is a Postdoctoral Fellow in the Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama.
Keisuke Yaku
Keisuke Yaku is a Postdoctoral Fellow in the Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama.
Keisuke Okabe
Keisuke Okabe is a Postdoctoral Fellow in the First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama.
Takashi Nakagawa
Takashi Nakagawa is Associate Professor in the Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama.