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Review
. 2021 Nov 9;12(11):1776.
doi: 10.3390/genes12111776.

NAD+ Metabolism and Diseases with Motor Dysfunction

Samuel Lundt  1   2 , Shinghua Ding  1   3
Affiliations
Review

NAD+ Metabolism and Diseases with Motor Dysfunction

Samuel Lundt et al. Genes (Basel). .

Abstract

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.

Keywords: NAD+; Nampt; energy metabolism; motor dysfunction; motor neuron diseases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
NAD+ structure (A) and biosynthetic pathways in mammalian cells (B). 3-HK: 3-Hydroxyl-Kynurenine; 3-HAA: 3-Hydroxyl-Anthranillic Acid; AMS: α-aminomuconate semialdehyde; MNAM: methyl-nicotinamide; NAR: Nicotinic Acid Riboside; NNMT: Nicotinamide N-methyltransferase; PA: Picolinic Acid; Pnp: Purine Nucleoside Phosphorylase; PRPP: Phosphoribosyl pyrophosphate.
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