The Influence of Nicotinamide on Health and Disease in the Central Nervous System

Fricker, Rosemary A.; Green, Emma L; Jenkins, Stuart I.; Griffin, Síle M.

doi:10.1177/1178646918776658

Cited by 156 publications

(121 citation statements)

References 119 publications

(174 reference statements)

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“…Plasmalogens were also found in decreased levels in our cohort in agreement with an earlier report [19]. The amide form of vitamin B3, nicotinamide, has been implicated in both neuroprotection and neuronal death [20]. Fig.…”

Section: Discussionsupporting

confidence: 93%

A metabolite‐based machine learning approach to diagnose Alzheimer‐type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

Stamate

Kim

Proitsi

et al. 2019

A&D Transl Res & Clin Interv

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Introduction Machine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer Disease (AD). Here we set out to test the performance of metabolites in blood to categorize AD when compared to CSF biomarkers. Methods This study analyzed samples from 242 cognitively normal (CN) people and 115 with AD‐type dementia utilizing plasma metabolites (n = 883). Deep Learning (DL), Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were used to differentiate AD from CN. These models were internally validated using Nested Cross Validation (NCV). Results On the test data, DL produced the AUC of 0.85 (0.80–0.89), XGBoost produced 0.88 (0.86–0.89) and RF produced 0.85 (0.83–0.87). By comparison, CSF measures of amyloid, p‐tau and t‐tau (together with age and gender) produced with XGBoost the AUC values of 0.78, 0.83 and 0.87, respectively. Discussion This study showed that plasma metabolites have the potential to match the AUC of well‐established AD CSF biomarkers in a relatively small cohort. Further studies in independent cohorts are needed to validate whether this specific panel of blood metabolites can separate AD from controls, and how specific it is for AD as compared with other neurodegenerative disorders.

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Section: Discussionsupporting

confidence: 93%

A metabolite‐based machine learning approach to diagnose Alzheimer‐type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

Stamate

Kim

Proitsi

et al. 2019

A&D Transl Res & Clin Interv

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“…A, K562 cells were treatment with 0.4 μg/mL DOX, 10 mM NAM or 0.4 μg/mL DOX + 10 mM NAM for 48 hours; K562R cells were treated with 6.5 μg/mL DOX, 10 mM NAM, or 6.5 μg/mL DOX + 10 mM NAM for 48 hours. There was no significant difference observed in the body weight of mice in each group, at the same time, combined with other reports [40][41][42] suggesting low toxicity and safety of NAM in mice, implicated the NAM potential value as clinically useful drugs in CML patients with drug resistance. The arrows indicate typical apoptotic cells with nuclear fragmentation.…”

Section: Discussionsupporting

confidence: 72%

Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1

Leng

Deng

et al. 2019

J of Cellular Biochemistry

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The NAD‐dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX‐resistant K562 cells (K562R) in a dose‐dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX‐induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX‐induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase‐3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.

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“…In addition, it is regarded as neuroprotectant primarily due to increasing the levels of NAD + [39]. Therefore, NAM could have a therapeutic role against trauma, ischemia, and neurodegeneration-Parkinson, Alzheimer, and Huntington diseases- [50] in addition to neuropsychological disorders including depression and schizophrenia [39,51]. Likewise, NAM could be beneficial against diabetes [52], HIV infection [53], and glaucoma [54].…”

Section: Nam Basic Principles and Metabolismmentioning

confidence: 99%

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

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The Influence of Nicotinamide on Health and Disease in the Central Nervous System

Cited by 156 publications

References 119 publications

A metabolite‐based machine learning approach to diagnose Alzheimer‐type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

A metabolite‐based machine learning approach to diagnose Alzheimer‐type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

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