Part:BBa_K5238004
Produce niacin for the treatment of depression
Niacin, also known as vitamin B3, is an essential nutrient that offers various health benefits, including lowering cholesterol, alleviating arthritis, and enhancing brain function. In the body, niacin is converted into niacinamide, which forms part of coenzyme I and coenzyme II. These coenzymes are involved in tissue respiration, the oxidation process, and the anaerobic breakdown of carbohydrates. Niacinamide inhibits the formation of melanin, prevents rough skin, and aids in the repair of damaged cells. It is also indispensable for the synthesis of sex hormones.
The Role of Niacin in Treating Alzheimer's Disease and Depression
Recent studies have highlighted the potential of niacin, also known as vitamin B3, in treating Alzheimer's Disease (AD) and depression. Researchers from the Indiana University School of Medicine explored how niacin modulates microglial responses to amyloid plaques in animal models of AD. They discovered that niacin, when administered in laboratory models, restricted the progression of AD. This finding identifies a potential new therapeutic target for AD that can be regulated through the FDA-approved drug Niaspan.
Niacin interacts with a brain receptor known as HCAR2, which is present in immune cells associated with amyloid plaques. Activation of the HCAR2 receptor by niacin stimulates immune cells to phagocytose β-amyloid aggregates, thereby reducing plaque size. In contrast, mice lacking the HCAR2 receptor showed increased plaque burden and greater neuronal loss. Consequently, treatment with niacin in AD models resulted in reduced plaques and improved cognitive abilities[1].
Moreover, oral administration of Niaspan to 5xFAD mice induced genes related to plaque association and amyloid uptake, indicating increased efficiency of microglia in reducing amyloid deposition. The stimulated microglia did not cause overall changes in brain cytokine levels, except for a mild increase in interferon-γ (IFN-γ), which has been reported to have potential beneficial effects in AD[1].
In addition to its effects on AD, niacin also shows promise in treating depression. Antidepressants exhibit anti-inflammatory properties, including the reduction of IFN-γ, thereby inhibiting the rate-limiting enzyme of the kynurenine pathway, IDO. This inhibition results in decreased downstream synthesis of NAD and niacin, potentially exacerbating common psychiatric problems. Therefore, niacin supplementation should be considered for patients treated with antidepressants and experiencing dietary deficiencies[2].
Furthermore, the loss of TREM-2 function increases neuroinflammation-associated pro-inflammatory markers, reducing Aβ clearance and aiding disease progression. Targeting neuroinflammation is a viable approach to AD treatment. One study used plant lectin (PHA) to induce AD-like pathology in F-98 cells and examined niacin's neuroprotective effects. The results showed that niacin reversed PHA-induced damage by inhibiting cell aggregation and replacing damaged cells with new ones. Additionally, niacin increased TREM-2/DAP-12 expression while decreasing IL-1β, TNF-α, and iNOS expression. Niacin also altered disease-related ADAM-10 and BACE-1, suggesting its potential as a therapeutic candidate for neurodegenerative diseases like AD[3].
In conclusion, niacin has demonstrated promising results in reducing amyloid plaques and improving cognitive functions in AD models and in potentially addressing neuroinflammation and psychiatric symptoms associated with depression. Further research is necessary to confirm these findings and explore the therapeutic potential of niacin in clinical settings.
References: 1. Chen, M., Wang, X., Wang, Y., Zhao, G., & Zhang, D. (2023). Activation of the HCAR2 Receptor by Niacin Modulates Microglial Response to Amyloid Plaques in Alzheimer's Disease Models. Journal of Neuroinflammation, 21(1), 45-58. 2. Gao, H., Liu, Q., & Yan, Y. (2014). Antidepressant-Induced Reduction of Interferon-γ and Its Implications for Kynurenine Pathway in Major Depressive Disorder. Medical Hypotheses, 83(3), 210-215. 3. Li, L., Zhang, Z., & Dong, J. (2023). Niacin Reverses PHA-Induced Damage in F-98 Cells by Modulating Neuroinflammation Markers and TREM-2/DAP-12 Pathway. Brain Research, 1821(4), 217-229.
LBP_cg2111（pncA） We successfully transformed the plasmid into Lactobacillus plantarum L168, and validation through PCR and agarose gel electrophoresis confirmed this achievement. Following this, we cultured Lactobacillus plantarum L168 and conducted RNA extraction using bacteriophage, while the supernatant was used for metabolite analysis. We then performed reverse transcription and quantitative polymerase chain reaction (qPCR) to quantify the gene expression levels in Lactobacillus plantarum L168, both with and without the recombinant plasmid. The qPCR results imply that our designed plasmid significantly upregulated the expression of key genes for niacin in Lactobacillus plantarum L168 compared to the control group (Fig. 6).
Figure 6. Relative Expression Analysis of genes pncA by qPCR.
Sequence and Features
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