## 3 Oxidative Stress Biomarkers Involved in Psoriasis Inflammation
### Sirtuins (SIRTs)  
Sirtuins are a family of highly conserved NAD+-dependent protein deacetylases that regulate physiological functions like metabolism, stress response, inflammation, and aging. Encoded by the SIRT1-7 genes in mammals, these enzymes exhibit tissue-specific expression patterns and diverse subcellular localization [38]. SIRT1 and SIRT2 are located in the cytoplasm and nucleus of the cell, whereas SIRT3-SIRT5 are found in the mitochondria, and SIRT6-SIRT7 are nuclear proteins [38]. In terms of function, SIRT1 controls signaling pathways linked to inflammation and suppresses oxidative stress, mitochondrial DNA mutation, mtROS, and mitochondrial damage. SIRT1, SIRT2, and SIRT6 regulate metabolism and lifespan by altering the NF-kB and fatty acid \(\beta\)-oxidation pathways, whereas SIRT3 enhances fatty acid \(\beta\)-oxidation and activates critical electron transport chain and urea cycle enzymes [39]. While SIRT7 is involved in DNA damage repair, inflammatory cytokine release, and cell survival, SIRT4 and SIRT5 activate enzymes that control cellular metabolism, such as the pyruvate dehydrogenase (PdH) complex and the glutamate dehydrogenase (GdH) complex in particular [40; 41]. Research used both in vitro and in vivo models, such as imiquimod-induced psoriasis in mice and TNF-stimulated HaCaT cells, to examine the expression levels and patterns of SIRTs in psoriasis. Dysregulation of sirtuin expression, observed in psoriasis with reductions in some (SIRT1-5) and increases in others (SIRT6, SIRT7), was reported to contribute to oxidative stress and inflammatory processes associated with the condition [42]. Additionally, the study revealed that SIRTs are mostly located in the epithelial layer, indicating that keratinocytes, acting as antigen-presenting cells instead of lymphocytes, might be the main immune response initiator [42]. Emerging evidence suggests that sirtuins, particularly SIRT1, may play a role in the pathogenesis of psoriasis, a chronic inflammatory skin disorder characterized by abnormal immune responses and skin cell proliferation. Through its ability to modulate the activity of transcription factors like NF-kB and AP-1, which are critical in controlling inflammatory responses, SIRT1 demonstrates anti-inflammatory capabilities and has been linked to guarding against oxidative stress-induced damage in psoriasis. By inhibiting pathways including MAPK, NF-kB, and STAT3, which are all linked to oxidative stress-induced inflammation, SIRT1 activation might potentially reduce inflammation in psoriatic skin [43]. According to research, skin biopsy specimens from psoriasis patients have altered SIRT expression, with significantly lower SIRT1 expression than control skin samples [44]. It is reported that nearly every nucleus in the epithelial layer of skin samples from healthy controls had a positive SIRT1 stain, whereas psoriatic samples were rare and with very weak staining showed this effect [44]. Other than that, the SIRT1 activator SRT2104 exhibits promise in mitigating psoriasis symptoms by reducing the expression of genes linked to inflammatory responses and skin cell differentiation, which are IL-17 and TNF-\(\alpha\)[18; 45; 46]. These results point to a possible therapeutic route for controlling psoriasis via SIRT-mediated pathways, indicating the need for more research into SIRT activators as cutting-edge psoriasis treatments. This shows that by focusing on oxidative stress and inflammatory pathways, sirtuins may provide therapeutic options for controlling psoriasis. Sirtuins may assist in preserving redox balance and shielding cells from oxidative damage in psoriasis, a condition where there is an imbalance between the generation of ROS and antioxidant defenses [47]. They achieve this by regulating the expression and activity of antioxidant enzymes and pro-oxidants [48]. Sirtuins protect cells from oxidative damage by balancing pro-oxidant radicals with antioxidant enzymes such glutathione peroxididases (GSH-pxs), CAT, and SOD [47; 48].