RESUMEN
The incidence of Alzheimer's disease (AD) is higher in people over the age of 65 and in African Americans (AA). Elevated acetylcholinesterase (AChE) activity has been considered a major player in the onset of AD symptoms. As a result, many FDA-approved AD drugs target AChE inhibition to treat AD patients. Hydrogen sulfide (H2S) is a signaling molecule known to downregulate oxidative stress and inflammation. The neutrophil-to-lymphocyte ratio (NLR) in the blood is widely used as a biomarker to monitor inflammation and immunity. This study examined the hypothesis that plasma AChE levels have a negative association with H2S levels and that a positive association exists between levels of NLR, HbA1c, and ROS with the AChE in the peripheral blood. The fasting blood sample was taken from 114 African Americans who had provided written informed consent approved by the IRB. The effect of H2S and high-glucose treatment on AChE activity levels was also investigated in THP-1 human monocytes. There was a significant negative relationship between AChE and the levels of H2S (r = -0.41, p = 0.001); a positive association between the levels of AChE with age (r = 0.26, p = 0.03), NLR (r = 0.23, p = 0.04), ROS (r = 0.23, p = 0.04) and HbA1c levels (r = 0.24, p = 0.04), in AA subjects. No correlation was seen between blood levels of AChE and acetylcholine (ACh). Blood creatinine had a negative correlation (r = -0.23, p = 0.04) with ACh levels. There was a significant effect of H2S on AChE inhibition and of high glucose in upregulating AChE activity in cultured monocytes. This study suggests hyperglycemia and lower H2S status can contribute to an increase in the AChE activity levels. Future clinical studies are needed to examine the potential benefits of supplementation with hydrogen sulfide pro-drugs/compounds in reducing the AChE and the cognitive dysfunctions associated with AD.
Asunto(s)
Enfermedad de Alzheimer , Sulfuro de Hidrógeno , Humanos , Sulfuro de Hidrógeno/farmacología , Acetilcolinesterasa/metabolismo , Hemoglobina Glucada , Monocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba , Neutrófilos/metabolismo , Negro o Afroamericano/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Sulfuros , Linfocitos/metabolismo , Inflamación/tratamiento farmacológico , GlucosaRESUMEN
Each cell controls when and how its genes must be expressed for proper function. Every function in a cell is driven by signaling molecules through various regulatory cascades. Different cells in a multicellular organism may express very different sets of genes, even though they contain the same DNA. The set of genes expressed in a cell determines the set of proteins and functional RNAs it contains, giving it its unique properties. Malfunction in gene expression harms the cell and can lead to the development of various disease conditions. The use of rapid high-throughput gene expression profiling unravels the complexity of human disease at various levels. Peripheral blood mononuclear cells (PBMC) have been used frequently to understand gene expression homeostasis in various disease conditions. However, more studies are required to validate whether PBMC gene expression patterns accurately reflect the expression of other cells or tissues. Vitamin D, which is responsible for a multitude of health consequences, is also an immune modulatory hormone with major biological activities in the innate and adaptive immune systems. Vitamin D exerts its diverse biological effects in target tissues by regulating gene expression and its deficiency, is recognized as a public health problem worldwide. Understanding the genetic factors that affect vitamin D has the potential benefit that it will make it easier to identify individuals who require supplementation. Different technological advances in gene expression can be used to identify and assess the severity of disease and aid in the development of novel therapeutic interventions. This review focuses on different gene expression approaches and various clinical studies of vitamin D to investigate the role of gene expression in identifying the molecular signature of the disease.
Gene optimizations are essential in maintaining biological functions. Gene dysregulation results in disease progression. Advanced analytical techniques determine the link between impaired genes and disease conditions. This knowledge can be applied to design clinical trials to aid novel therapeutic interventions and disease prevention.