RESUMEN
Alzheimer's disease (AD) is a primary cause of dementia. The complement system is closely related to AD pathology and may be a potential target for the prevention and treatment of AD. In our study, we conducted a bioinformatics analysis to analyze the role of the complement system and its related factors in AD using Gene Expression Omnibus (GEO) data. We also conducted a functional analysis. Our study verified that 23 genes were closely related to differentially expressed complement system genes in diseases after intersecting the disease-related complement system module genes and differentially expressed genes. The STRING database was used to predict the interactions between the modular gene proteins of the differential complement system. A total of 21 gene proteins and 44 interaction pairs showed close interactions. We screened key genes and created a diagnostic model. The predictive effect of the model was constructed using GSE5281 and our study indicated that the predictive effect of the model was good. Our study also showed enriched negative regulation of Notch signaling, cytokine secretion involved in the immune response pathway, and cytokine secretion involved in immune response hormone-mediated apoptotic signaling pathway. We hope that our study provides a promising target to prevent and delay the onset, diagnosis, and treatment of AD.
Asunto(s)
Enfermedad de Alzheimer , Perfilación de la Expresión Génica , Humanos , Mapas de Interacción de Proteínas/genética , Enfermedad de Alzheimer/genética , Transducción de Señal , Biología Computacional , CitocinasRESUMEN
BACKGROUND: MicroRNA (miR)-125a-3p is reported to play an important role in some central nervous system diseases, such as Alzheimer's disease (AD). However, a study has not been conducted on the mechanism of miR-125a-3p in the pathological process of AD. METHODS: First, we assessed the expression of miR-125a-3p in AD cohort. Subsequently, we altered the expressions of miR-125a-3p to assess its role in cell viability, cell apoptosis, amyloid-ß (Aß) metabolism, and synaptic activity. Finally, we identified its potential mechanism underlying AD pathology. RESULTS: This study unveiled the potential function of miR-125a-3p through modulating amyloid precursor protein processing. Additionally, miR-125a-3p influenced cell survival and activated synaptic expression through the modulation of Aß metabolism in the mitogen-activated protein kinase (MAPK) pathway via fibroblast growth factor receptor 2. CONCLUSION: Our study indicates that targeting miR-125a-3p may be an applicable therapy for AD in the future. However, more in vitro and in vivo studies with more samples are needed to confirm these results.
Asunto(s)
Enfermedad de Alzheimer , MicroARNs , Humanos , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Precursor de Proteína beta-Amiloide/genéticaRESUMEN
BACKGROUND: Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD. OBJECTIVE: Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOEÉ4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI). METHODS: All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls. RESULTS: The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus. CONCLUSION: There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOEÉ4 allele effects.