NAD+ Degrading Enzymes, Evidence for Roles During Infection

Tan, Arnold; Doig, Craig

doi:10.3389/fmolb.2021.697359

Cited by 18 publications

(13 citation statements)

References 282 publications

(325 reference statements)

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“…There are nuclear receptors that activate NAD + . These transcription factors regulate the expression of genes involved in NAD + biosynthesis or consumption (41)(42). NAD + is a cofactor for various enzymatic reactions and a substrate for NAD + -dependent enzymes such as sirtuins, poly-ADP-ribose polymerases, and cyclic ADP-ribose (cADPR) synthases.…”

Section: Resultsmentioning

confidence: 99%

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Raghavan¹

2023

Preprint

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There are seven sirtuin genes in humans that encode seven sirtuin enzymes (SIRT1–7), each of which has unique functions and subcellular locations. Sirtuins are NAD+-dependent protein deacetylases that play a significant role in physiological processes such as energy metabolism, stress responses, DNA repair, and gene expression. Sirtuins are essential targets for aging-related diseases such as type 2 diabetes, inflammatory diseases, and neurodegenerative disorders. However, finding a single molecule that can activate all seven sirtuin genes is challenging because each isoform has a unique structure, substrates, and regulatory mechanisms. Most known sirtuin activators are specific for SIRT1, the most studied isoform of the sirtuin family. Here, we report that Metadichol®, a nano-emulsion of long-chain alcohols, induces 3- to 15-fold expression of all SIRT1–7 genes in human dermal fibroblasts when used in concentrations ranging from 1 pg/mL to 100 ng/mL. SIRT3 and FOXO1 gene expressions were 15-fold higher than those after treatment with Metadichol®. In addition, KL, FOXO1, TERT, and TP53 exhibited increased expression. Sirtuins and the four genes regulate aging, metabolism, and DNA repair and are age-related diseases like cancer, cardiovascular disease, and diabetes. All of these genes play essential roles in improving the quality of life as we age.

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Section: Resultsmentioning

confidence: 99%

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Raghavan¹

2023

Preprint

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“…Excessive consumption of NAD+ damages cellular attempts to maintain homeostasis. During immune challenge, activation of NAD+ degrading enzymes serve as a fundamental driver of NAD+ depletion (Tan & Doig, 2021). For example, Herpes simplex virus 1 infection triggers multiple changes in the metabolism of host cells, including a dramatic decrease in the levels of NAD+ (Grady, Hwang, Vastag, Rabinowitz, & Shenk, 2012), while a model coronavirus infection was shown to drive down cellular NAD+ and NADP+ levels in infected cells (Heer et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Viewing teratogens through the lens of nicotinamide adenine dinucleotide (NAD+)

Mark

Dunwoodie

2022

Birth Defects Research

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Background Nicotinamide adenine dinucleotide (NAD+) depletion is associated with numerous diseases in humans. Recently it was revealed that genetic blockage of the NAD+ synthesis pathway in humans causes birth defects in multiple organ systems and miscarriage. Additionally, mice with NAD+ deficiency created through dietary restriction of tryptophan and vitamin B3 were shown to have congenital anomalies affecting virtually every organ system along with miscarriage. Perturbations in NAD+/NADH affect mechanisms of teratogenesis presented by Wilson and others, including genetic alterations, altered energy sources, and lack of precursors and substrates needed for biosynthesis. Methods Medical literature was evaluated to demonstrate how perturbations in NAD+/NADH affect mechanisms of teratogenesis. In addition, literature describing several different teratogens of various types (infectious, physical, maternal health factors, drugs) was reviewed showing the impact of these teratogens on NAD+ and NAD+/NADH ratios. Result Many teratogens affect NAD+ by altering its metabolism, decreasing its intracellular availability, or decreasing its production, which in turn is a plausible mechanism for the creation of birth defects. Conclusion Looking at teratogens through the lens of their impact on NAD+ could provide valuable insight into the mechanism by which some teratogens cause birth defects and miscarriage.

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“…Ultimately, during the catabolic phase of the SSP, e.g. SARS-CoV-2 related sepsis, quantum biosemiotics phase coherence is thought to fail on multiple scales of time and space, resulting in genomic instability, loss of redox homeostasis, hijacked energy metabolism during infection [11,15,39,251,252], loss of glycosidic anomeric fidelity (e.g. loss of antigenic determinants), immune dysfunction, and a consumptive coagulopathy of the microvasculature [10,[12][13][14] .…”

Section: Preventing the Postulated Catabolic Hydrolytic Phase Of The ...mentioning

confidence: 99%

“…the catabolic, hydrolytic phase of the SSP, would likely occur more readily in patients suffering from subclinical or clinically-marginal scurvy [11,[13][14][15]241] . Moreover, the combination of NAD+ depletion and L-ascorbic acid deficiency is likely to predispose to impaired innate immune response [251,252] . Baseline preinfectious levels of NAD+ and L-AA, along with various other micro-nutrient levels, might result in some observed clinical variability of the temporal component of priming and provocation inoculations of the SSP.…”

Section: Preventing the Postulated Catabolic Hydrolytic Phase Of The ...mentioning

confidence: 99%

“…It remains to be seen whether a combination of empiric NAD+ repletion and L-ascorbic acid supplementation may have synergistic therapeutic and/or preventative benefit, clinically. Empiric NAD+ repletion [251,252], L-ascorbic acid (L-AA) supplementation, and bioflavonoid (e.g. quercetin) administration might be considered as primary prevention.…”

Section: Ensemble Hcc -A Supramolecular Biological Strategy To Combat...mentioning

confidence: 99%

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Are the mRNA vaccines inducing the Sanarelli-Shwartzman phenomenon?

Davidson¹,

Winey²

2022

GSC Adv. Res. Rev.

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Adverse events of myocarditis, pericarditis, and thrombosis, temporally associated with mRNA vaccination(s) and/or mRNA vaccine boosters, have been reported during post-marketing safety surveillance in the U.S. CDC VAERS database and 2021 CDC guidance to physicians. An interim report unexpectedly revealed inflammatory biomarker elevations in vaccine recipients. During review of considerable published research on the Sanarelli-Shwartzman phenomenon (SSP) and the use of nucleic acids as vaccine adjuvants, a novel, hypothesis is proposed. Even today, after being studied for over a century, the pathophysiology of the SSP is not fully understood. Motivated by a paper from 1950, titled “General Adaptation Syndrome” by Hans Selye, and recent published research by Korean investigators, a novel, non-conventional hypothesis was generated. Gluten and lectin sensitivity are cited as examples of sensitizing events of the SSP, for which we propose ensemble hydrophobic chiroptical catalysis may have therapeutic benefit. Under the ensemble HCC hypothesis, we propose that inflammatory stress and scurvy promote loss of chirality control, anomeric fidelity, phenotypic stability, and immune function, both humoral and cell-mediated, with the dialyzable transfer factor, L-ascorbic acid, and spin water playing central roles. It is proposed that therapeutic synergy of L-ascorbic acid, bioflavonoids, and corticosteroids in countering the SARS-CoV-2 pathogen arises from memory of chirality which originated during their biosynthesis. It is proposed that ensemble HCC is powered by radiant and or zero-point energy (quantum vacuum fluctuations) which may support a paradigm shift to supramolecular biology. The distinction between supramolecular biology and supramolecular xenobiology is highlighted.

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NAD+ Degrading Enzymes, Evidence for Roles During Infection

Cited by 18 publications

References 282 publications

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Viewing teratogens through the lens of nicotinamide adenine dinucleotide (NAD+)

Are the mRNA vaccines inducing the Sanarelli-Shwartzman phenomenon?

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