NAD+ homeostasis in health and disease

Abstract

AD, the first cofactor described, was discovered in 1906 (ref. 1 ), when it was observed that yeast juice separated into low-and high-molecular-weight fractions lost the capacity to perform alcoholic fermentation. However, addition of the lowmolecular-weight fraction to yeast accelerated the fermentation reaction, even if it was boiled beforehand. This observation suggested that a yet-unknown heat-stable factor present in the lowmolecular-weight fraction was required for fermentation. At that time, this factor was named 'cozymase' . Almost three decades later, the chemical composition of cozymase, comprising an adenine, a phosphate and a reducing-sugar group, was reported 2 . The actual function of NAD + , however, remained unclear until 1936, when cozymase was shown to be capable of transferring hydride between molecules with the nicotinamide base as its redox site 3 . This research on NAD + was rewarded by three Nobel prizes. In the early 2000s, interest in NAD + experienced a resurrection, after a novel role of NAD + as a cosubstrate for the sirtuin enzyme family, important regulators of longevity and metabolism, was discovered 4-6 .Brain 98 NMNaT3Testis 307 Intestine, spleen, brain, SM, lung, pancreas, blood, WaT 98,307

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1α Signaling Pathways Mediated by the NAMPT-NAD Pathway

“…Knowingly, a critical reduction of regional cerebral blood flow or severe oxygen and glucose deprivation leads to mitochondrial dysfunction within minutes after ischemia [ 11 , 12 ], which could trigger mitochondrial quality control [ 9 ], including ROS scavenging, mitochondrial dynamics, and mitophagy [ 11 , 12 , 17 ]. Meanwhile, the related study demonstrates that depletion of ATP production is one of the major initiators, which triggers ischemic cascades, such as membrane ion pump failure, efflux of cellular potassium, influx of sodium, and membrane depolarization.…”

“…NAD+, as a coenzyme, plays a vital role in energy balance and cellular redox reactions in ischemic stroke [ 50 – 52 ]. In the cytosol, NAD is translated to NADH during glycolysis, and the tricarboxylic acid cycle (TAC) enzymes reduce the NAD+ molecules [ 9 , 52 ]. Under the hypoxia-ischemia conditions, NADH gets oxidized in the cytoplasm via the reduction of pyruvate to lactate ( Figure 6 ), which leads to mitochondria dysfunction and NAD decrease.…”

Energy Metabolism Decline in the Aging Brain; Pathogenesis of Neurodegenerative Disorders

“…Humans depend primarily on vitamin B3 as a precursor for nicotinamide adenine dinucleotide (NAD) synthesis [42]. NAD is the main coenzymes in redox reactions in mitochondria [43][44][45]. During the reduction of NAD, the molecule acquires two electrons and one proton, while the second proton is released into the cytoplasm.…”

“…In a normal healthy brain, the level of NAD exceeds its neuronal needs [47]. The level, however, declines with age and particularly is reduced in various chronic diseases [40,45,47].…”

Spatio-temporal heterogeneity in hippocampal metabolism in control and epilepsy conditions

“…NADPH and NADH have similar optical properties, therefore it is expected that NADPH may contribute to the total autofluorescence signal. Because the cellular NADP + / NADPH pool is about one order of magnitude lower than the NAD/NADH pool, in the present study we assume that short-term variations of experimentally detected fluorescent changes responses account for variations in NADH 44 . In the present study, we use the term NAD(P)H for the fluorescent signal.…”