Journal of Energy Bioscience 2025, Vol.16, No.1, 31-41 http://bioscipublisher.com/index.php/jeb 36 therapeutic idea, and their sensitivity to oxidative stress can be used to fight tumors (Ju et al., 2020). NADPH oxidases are also involved in the occurrence of many diseases, such as cardiovascular disease and neurodegenerative diseases. It participates in the processes of these diseases by producing ROS and regulating signaling pathways (Chan et al., 2009 ; Maraldi et al., 2021). 6 NADPH Deficiency and Its Implications 6.1 Diseases associated with NADPH deficiency NADPH deficiency is closely related to an immune disease called chronic granulomatous disease (CGD). CGD is a congenital immunodeficiency disease that is mainly caused by malfunction of NADPH oxidase in phagocytes. When this enzyme does not work properly, it cannot produce enough reactive oxygen species (ROS), which are used to kill bacteria and fungi. This makes people more susceptible to repeated infections and the symptoms are more severe (Stasia and Li, 2008; Arnold and Heimall, 2017; Yu et al., 2020). The cause of CGD is usually a genetic mutation in certain subunits of NADPH oxidase, such as CYBB (gp91phox), NCF1 (p47phox) and CYBA (p22phox) (Stasia and Li, 2008; Yu et al., 2020). These patients not only have infection problems, but are also prone to inflammation, such as granulomas or intestinal inflammatory diseases (Arnold and Heimall, 2017; Yu et al., 2020; León-Lara et al., 2021). In addition, some CGD patients and women with X-linked mutations also develop autoimmune diseases (Yu et al., 2020). 6.2 Impact of NADPH levels on immune function and disease progression NADPH is important for the functioning of the immune system, especially in phagocytes. It helps these cells to perform an "oxidative burst," a step that is necessary to kill pathogens. If NADPH oxidase activity is insufficient, cells will have difficulty clearing bacteria or viruses, making them more susceptible to infection (Hohn and Lehrer, 1975; Giardino et al., 2017; Violi et al., 2017). Not only that, this deficiency can also make inflammation excessive because cells cannot properly regulate and shut down related signaling pathways. Studies have found that lack of NADPH activates the NF-κB pathway and increases pro-inflammatory factors, resulting in chronic inflammation and even tissue damage (Segal et al., 2010; Segal et al., 2012; León-Lara et al., 2021). In addition, some studies have shown that even a small amount of residual activity of NADPH oxidase can affect the severity of the disease and the life expectancy of patients, indicating that maintaining a certain level of NADPH is really important (Stasia and Li, 2008; Yu et al., 2020). 6.3 Therapeutic interventions to enhance NADPH availability Currently, there are some ways to try to solve the problem of NADPH deficiency. Hematopoietic stem cell transplantation (HSCT) is currently the only cure for CGD, especially for children, with a survival rate of more than 90% (Arnold and Heimall, 2017; Yu et al., 2020). Gene therapy is also a developing direction. This method is to re-implant the repaired hematopoietic stem cells into the body in the hope of restoring the function of NADPH oxidase. Although the effect is not stable enough at present, many clinical trials are being improved in order to achieve a more lasting therapeutic effect (Barese et al., 2004; Yu et al., 2020). In addition to these, there are some drugs under study. These drugs mainly target inflammation or oxidative stress caused by CGD, such as pioglitazone, tamoxifen and rapamycin, which can help control symptoms (Yu et al., 2020; León-Lara et al., 2021). There is also a new class of compounds, such as CDDO-Im (belonging to triterpenes), which can activate anti-inflammatory pathways and are independent of NADPH oxidase. This type of drug shows the potential to reduce inflammation in CGD models (Segal et al., 2010). 7 NADPH in Immune Response and Cellular Defense 7.1 Examination of NADPH's role in immune cell function, particularly in phagocytes NADPH is very important in immune cells, especially in phagocytes, such as neutrophils and macrophages. It helps these cells produce reactive oxygen species (ROS) to kill invading pathogens. There is an enzyme called NADPH oxidase on the membrane of these cells, which can rapidly release ROS in a respiratory burst. This burst is critical for phagocytes to eliminate the bacteria or fungi they ingest (Thomas, 2017; Moghadam et al., 2021; Vermot et al., 2021). NADPH oxidase is not a single molecule, but a complex composed of several parts. It
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