The Role of Nicotinamide Adenine Dinucleotide in the Pathogenesis of Rheumatoid Arthritis: Potential Implications for Treatment

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease characterised by small joint swelling, deformity, and dysfunction. Its exact aetiology is unclear. Current treatment approaches do not control harmful autoimmune attacks or prevent irreversible damage without considerable side effects. Nicotinamide adenine dinucleotide (NAD+), an important hydrogen carrier in mitochondrial respiration and oxidative phosphorylation, is the major determinant of redox state in the cell. NAD+ metabolites act as degradation substrates for a wide range of enzymes, such as sirtuins, poly-ADP-ribose polymerases, ADP-ribosyltransferases, and CD38. The roles of NAD+ have expanded beyond its role as a coenzyme, linking cellular metabolism to inflammation signalling and immune response. The aim of this review is to illustrate the role of NAD+-related enzymes in the pathogenesis of RA and highlight the potential therapeutic role of NAD+ in RA.

Interleukin -37 in rheumatoid arthritis: Correlation with clinical severity and genetic polymorphisms in Mosul city, Iraq

“…In favor of this, we found that the mean IL-37 level was varied greatly in both RA patients and normal individuals among different studies. This ranged from as low as (28.83 ng/l in RA and 11.84 in the controls) in one study 44 to as high as (712.40 ng/l in RA and 133.50 in the controls) in another study, 37 2) Some elements of the DAS 28 scoring system such as the number of tender and swelling joints and the overall health condition of the patients are largely subjected to personal judgement of the physicians which might affect the calculation of DAS28 score, 3) Differences in cohorts is another possibility, so a larger cohort might explore more positive correlation, 4) Most of the studies that reveled a positive correlation between IL-37 and DAS28 were carried on Asian populations (China) and only one study was reported among Arab population (Egypt). 45 Therefore, ethnicity is an important suggested factor to be considered when interpreting IL-37 results, 5) The concentration of IL-37 was observed to be significantly higher in the aspirated synovial fluid of RA patients than the circulation 45 and therefore synovial IL-37 might be a better marker to be considered when correlated with DAS 28 score, 6) Finally, in the current study we did not take into consideration the effect of the drugs on the IL-37 level which might be considered one of the limitations of this study.…”

Fingerstick blood assay maps real-world NAD+ disparity across gender and age

“…Blood NAD + level is becoming an important physiological parameter for evaluating NAD + boosting strategies. Several previously reported clinical studies of NAD + supplementation established that blood NAD + content decreases with the progression of age-related diseases such as mitochondrial myopathy and rheumatoid arthritis 7,32 .…”

“…Blood NAD + level is becoming an important physiological parameter for evaluating NAD + boosting strategies. Several previously reported clinical studies of NAD + supplementation established that blood NAD + content decreases with the progression of age-related diseases such as mitochondrial myopathy and rheumatoid arthritis 7,32 . In addition, previous studies showed that oral supplementation of NA 12 , NR 33–35 or NMN 17,36 can increase the blood NAD + level and lead to beneficial outcomes.…”

“…NAD + is an essential substrate for numerous redox reactions and regulatory proteins including poly(ADP-ribose) polymerase (PARPs), Sirtuins, CD38/157 and SARMs, which play important roles in DNA repair, protein deacetylation, immune response, and other fundamental cellular processes [1][2][3][4][5] . The decline of NAD + content in blood and saliva has been associated with aging and age-related symptoms such as frailty 4,6 , rheumatoid arthritis 7,8 , and heart failure 9,10 at old age. In addition, oral administration of NAD + precursors as a potential intervention strategy of age-related symptoms has been demonstrated in clinical trials to improve body NAD + levels 5,[11][12][13][14][15] , muscle functions and skeletal muscle insulin sensitivity and signaling 16,17 , establishing NAD + level as an emerging indicator of healthy aging.…”

Fingerstick blood assay maps real‐world NAD+ disparity across gender and age

“…In blood, NAD + is enriched in erythrocytes compared to serum and white blood cells (Chaleckis et al, 2014 ; Chaleckis, Murakami, Takada, Kondoh, & Yanagida, 2016 ; Clement, Wong, Poljak, Sachdev, & Braidy, 2019 ). The decline of NAD + content in blood cells (Chaleckis et al, 2016 ), muscle (Zhang et al, 2016 ), and saliva (Teruya, Goga, & Yanagida, 2021 ) has been associated with aging and age‐related symptoms such as frailty (Covarrubias et al, 2021 ; Kumar et al, 2014 ), rheumatoid arthritis (Busso et al, 2008 ; Weiqian, Caihong, & Jin, 2018 ), and heart failure (Carpenter & Dierickx, 2022 ; Yuan et al, 2022 ) at old age. In addition, oral administration of NAD + precursors as a potential intervention strategy of age‐related symptoms has been demonstrated in clinical trials to improve body NAD + levels (Chini et al, 2018 ; Imai et al, 2000 ; Khan et al, 2014 ; Pirinen et al, 2020 ; Rajman et al, 2018 ; Yoshino, Baur, & Imai, 2018 ), muscle functions, and skeletal muscle insulin sensitivity and signaling (Goody & Henry, 2018 ; Yoshino et al, 2021 ), establishing NAD + level as an emerging indicator of healthy aging.…”