Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
Interdisciplinary Neuroscience Program, University of Missouri-Columbia, Columbia, MO 65211, USA.
Genes (Basel). 2021 Nov 9;12(11):1776. doi: 10.3390/genes12111776.
Neurodegenerative diseases result in the progressive deterioration of the nervous system, with motor and cognitive impairments being the two most observable problems. Motor dysfunction could be caused by motor neuron diseases (MNDs) characterized by the loss of motor neurons, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease, or other neurodegenerative diseases with the destruction of brain areas that affect movement, such as Parkinson's disease and Huntington's disease. Nicotinamide adenine dinucleotide (NAD) is one of the most abundant metabolites in the human body and is involved with numerous cellular processes, including energy metabolism, circadian clock, and DNA repair. NAD can be reversibly oxidized-reduced or directly consumed by NAD-dependent proteins. NAD is synthesized in cells via three different paths: the de novo, Preiss-Handler, or NAD salvage pathways, with the salvage pathway being the primary producer of NAD in mammalian cells. NAD metabolism is being investigated for a role in the development of neurodegenerative diseases. In this review, we discuss cellular NAD homeostasis, looking at NAD biosynthesis and consumption, with a focus on the NAD salvage pathway. Then, we examine the research, including human clinical trials, focused on the involvement of NAD in MNDs and other neurodegenerative diseases with motor dysfunction.
神经退行性疾病导致神经系统的进行性恶化，运动和认知障碍是两个最明显的问题。运动功能障碍可能由运动神经元疾病（MNDs）引起，这些疾病的特征是运动神经元的丧失，如肌萎缩侧索硬化症和夏科-马里-图思病，或其他影响运动的大脑区域受损的神经退行性疾病，如帕金森病和亨廷顿病。烟酰胺腺嘌呤二核苷酸（NAD）是人体内含量最丰富的代谢物之一，参与许多细胞过程，包括能量代谢、生物钟和 DNA 修复。NAD 可以通过可逆氧化-还原或直接被 NAD 依赖性蛋白消耗。细胞内通过三种不同途径合成 NAD：从头合成途径、普赖斯-哈彻尔途径或 NAD 补救途径，补救途径是哺乳动物细胞中 NAD 的主要产生途径。NAD 代谢被认为与神经退行性疾病的发展有关。在这篇综述中，我们讨论了细胞内 NAD 动态平衡，研究了 NAD 的生物合成和消耗，重点关注 NAD 补救途径。然后，我们研究了 NAD 在 MND 和其他运动功能障碍的神经退行性疾病中的作用，包括人类临床试验。
