Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities.Neuroinflammatory plaques formed through the extracellular deposition of amyloid-βproteins,a...Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities.Neuroinflammatory plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's disease.Besides symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease progression.MicroRNAs(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes.Indeed,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several pathways.Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder.Mi R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's disease.It has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other mRNAs.Regarding the impact on glial cells,miR-146a also exhibits differential effects.On one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons.In this review,we provide a comprehensive analysis of the involvement of miR-146a in the pathogenesis of Alzheimer's disease.We aim to elucidate the relationship between miR-146a and the key pathological manifestations of Alzheimer's disease,such as amyloid-βdeposition,tau protein hyperphosphorylation,neuronal death,mitochondrial dysfunction,synaptic dysfunction,and glial cell dysfunction,as well as summarize recent relevant studies that have highlighted the potential of miR-146a as a clinical diagnostic marker and therapeutic target for Alzheimer's disease.展开更多
BACKGROUND： Intracerebral hemorrhage（ICH） and coronary heart disease （CHD） have the same pathological base, atherosclerosis, and the similar risk factors,such as smoking ,drinking, hypertension, hyperlipemia, dia...BACKGROUND： Intracerebral hemorrhage（ICH） and coronary heart disease （CHD） have the same pathological base, atherosclerosis, and the similar risk factors,such as smoking ,drinking, hypertension, hyperlipemia, diabetes mellitus, etc; but the distributions of two diseases are very different in the populations. This may be related to the exposure of risk factors and different effects of risk factors on two diseases. OBJECTIVE： To analyze the distribution difference of risk factors for ICH and CHD in the populations of Tongliao city of Nei Monggol Autonomous Region. DESIGN： Retrospective analysis. SETTING： School of Radiation Medicine and Public Health, Soochow University; Tongliao Hospital, Nei Monggol Autonomous Region. PARTICIPANTS： Random sampling was used to select 6 hospitals from 10 hospitals affiliated to Tongliao City of Nei Monggol Autonomous Region. Totally 1 672 medical records of patients with ICH and 2 195 medical records of patients with CHD admitted to Department of Neurology and Department of Cardiovascular Internal Medicine of above-mentioned 6 hospitals between January 2003 and December 2005 were collected according to the investigation need. METHODS： The subjects, whose medical records were involved, were performed retrospective analysis with pre-prepared questionnaire ＂Stroke and Coronary Heart Disease Epidemiologic Questionnaire＂. The main contents included： ①Social demography condition： The distributions of gender, age, nationality, etc. ②Previous history of disease： hypertension, diabetes mellitus, etc. ③Related risk factors： systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking, drinking and glucose （GLU）. The database of Epidata was transformed to SPSS database. Single-and multiple-factor non-conditional Logistic regression analysis were performed on the data, and OR value and 95% CI were calculated. The distribution differences of risk factors for two diseases were compared. MAIN OUTCOME MEASURES： Single- and multi-factor non-conditional Logistic regression analysis results of each factor of patients. RESULTS： Single-factor non-conditional Logistic regression analysis showed that statistical significance existed in gender, age, nationality, smoking, drinking, history of hypertension, history of diabetes mellitus, hypertension, triglyceride （TG）, and GLU ten factors（OR =0.199, OR 95% CI 0.142-0.280 to OR =7.484, OR 95% CI 6.186-9.054, P 〈 0.01）. ②The results of multiple-factor non-conditional Logistic regression analysis showed 8 factors including age, gender, smoking, hypertension, history of hypertension, history of diabetes mellitus, GLU and TG（OR =0.203, OR 95% CI 0.114-0.361 to OR =8.262,OR 95% CI 5.466- 12.491, P 〈 0.01）. CONCLUSION： ICH and CHD are the diseases induced by various risk factors. Significant difference exists in gender, age, smoking, hypertension, history of hypertension, GLU, history of diabetes mellitus and TG.展开更多
基金supported by the National Natural Science Foundation of China,No.81970991(to GC)Program of Shanghai Academic Research Leader,No.22XD1423400(to HG)。
文摘Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities.Neuroinflammatory plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's disease.Besides symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease progression.MicroRNAs(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes.Indeed,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several pathways.Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder.Mi R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's disease.It has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other mRNAs.Regarding the impact on glial cells,miR-146a also exhibits differential effects.On one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons.In this review,we provide a comprehensive analysis of the involvement of miR-146a in the pathogenesis of Alzheimer's disease.We aim to elucidate the relationship between miR-146a and the key pathological manifestations of Alzheimer's disease,such as amyloid-βdeposition,tau protein hyperphosphorylation,neuronal death,mitochondrial dysfunction,synaptic dysfunction,and glial cell dysfunction,as well as summarize recent relevant studies that have highlighted the potential of miR-146a as a clinical diagnostic marker and therapeutic target for Alzheimer's disease.
文摘BACKGROUND： Intracerebral hemorrhage（ICH） and coronary heart disease （CHD） have the same pathological base, atherosclerosis, and the similar risk factors,such as smoking ,drinking, hypertension, hyperlipemia, diabetes mellitus, etc; but the distributions of two diseases are very different in the populations. This may be related to the exposure of risk factors and different effects of risk factors on two diseases. OBJECTIVE： To analyze the distribution difference of risk factors for ICH and CHD in the populations of Tongliao city of Nei Monggol Autonomous Region. DESIGN： Retrospective analysis. SETTING： School of Radiation Medicine and Public Health, Soochow University; Tongliao Hospital, Nei Monggol Autonomous Region. PARTICIPANTS： Random sampling was used to select 6 hospitals from 10 hospitals affiliated to Tongliao City of Nei Monggol Autonomous Region. Totally 1 672 medical records of patients with ICH and 2 195 medical records of patients with CHD admitted to Department of Neurology and Department of Cardiovascular Internal Medicine of above-mentioned 6 hospitals between January 2003 and December 2005 were collected according to the investigation need. METHODS： The subjects, whose medical records were involved, were performed retrospective analysis with pre-prepared questionnaire ＂Stroke and Coronary Heart Disease Epidemiologic Questionnaire＂. The main contents included： ①Social demography condition： The distributions of gender, age, nationality, etc. ②Previous history of disease： hypertension, diabetes mellitus, etc. ③Related risk factors： systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking, drinking and glucose （GLU）. The database of Epidata was transformed to SPSS database. Single-and multiple-factor non-conditional Logistic regression analysis were performed on the data, and OR value and 95% CI were calculated. The distribution differences of risk factors for two diseases were compared. MAIN OUTCOME MEASURES： Single- and multi-factor non-conditional Logistic regression analysis results of each factor of patients. RESULTS： Single-factor non-conditional Logistic regression analysis showed that statistical significance existed in gender, age, nationality, smoking, drinking, history of hypertension, history of diabetes mellitus, hypertension, triglyceride （TG）, and GLU ten factors（OR =0.199, OR 95% CI 0.142-0.280 to OR =7.484, OR 95% CI 6.186-9.054, P 〈 0.01）. ②The results of multiple-factor non-conditional Logistic regression analysis showed 8 factors including age, gender, smoking, hypertension, history of hypertension, history of diabetes mellitus, GLU and TG（OR =0.203, OR 95% CI 0.114-0.361 to OR =8.262,OR 95% CI 5.466- 12.491, P 〈 0.01）. CONCLUSION： ICH and CHD are the diseases induced by various risk factors. Significant difference exists in gender, age, smoking, hypertension, history of hypertension, GLU, history of diabetes mellitus and TG.
