Moreover, supplementing the high active extracellular NAMPT (eNAMPT) also increases NAD + biogenesis and aging-related symptoms 15, 16, 17. Consequently, the NAMPT enhancers can effectively increase NAD + levels and prevent neuronal degeneration 12, 13, 14. As NAMPT activity decreases with age, it results in NAD + depletion and cognitive impairment 11. In mammalian cells, most NAD + precursors were “reclaimed” to NAD + via the rate-limiting enzyme nicotinamide phosphoribosyl transferase (NAMPT) of the salvage pathway. Previous studies showed that supplementing NAD + precursors, such as nicotinamide mononucleotide (β-NMN), nicotinamide riboside (NR), nicotinamide (NAM), or Niacin (NA), were efficient for anti-aging 8, 9, 10. To counteract this, two strategies have been proposed: reducing the activity of NAD +-consuming enzymes 6, 7 and increasing the biosynthesis of NAD + by supplying NAD + precursors and activating NAD + synthetic enzymes. However, with advancing age, the equilibrium of NAD + homeostasis is impaired, leading to a considerable decline, correlating with age-related defects 1, 2, 3, 4, 5. Nicotinamide adenine dinucleotide (NAD) homeostasis is organized and coordinated in many physiological statuses. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD + salvage pathways and improve age-related symptoms. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD + synthesis. Nicotine, a metabolite of the NAD + metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Not for resale without express authorization.Imbalances in NAD + homeostasis have been linked to aging and various diseases. Since GAPDH is expressed at high levels in most tissues, it is useful as protein loading control in Western Blot analysis.įor Research Use Only. Associations between GAPDH, actin and tubulin have also be reported. GAPDH is reported to bind to a variety of other proteins, including the amyloid precursor protein, mutations in which cause some forms of Alzheimer's disease (AD), and the polyglutamine tracts of Huntingtin, the protein product aberrant forms of which are causative of Huntington's disease. Further, GAPDH is involved in other cellular processes ranging from membrane fusion, and neuronal apoptosis in cancer. Studies provide evidence of GAPDH playing an essential part in gene expression observed in apoptosis and as part of the cellular phenotype of age-related neurodegenerative diseases. GAPDH is reported to be involved in the processes of DNA replication, DNA repair, nuclear RNA export, membrane fusion and microtubule bundling. Apart from playing a key role in glycolysis, GAPDH is ubiquitously expressed and displays other activities unrelated to its glycolytic function. GAPDH exists as a tetramer of identical 37-kDa subunits and catalyzes the reversible reduction of 1,3-bisphosphoglycerate to glyceraldehyde 3-phosphophate in the presence of NADPH. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) is a catalytic enzyme commonly known to be involved in glycolysis.
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