检索结果-南通市图书馆

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

引用

Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： zhimin long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Liquiritigenin promotes osteogenic differentiation and prevents bone loss via inducing auto-lysosomal degradation and inhibiting apoptosis

引用

Genes & Diseases 2023年第1期10卷 284-300页

作者： Yu Qiu Yueyang Zhao zhimin long Aijia Song Peng Huang Kejian Wang Ling Xu David Paul Molloy Guiqiong He College of Stomatology Chongqing Medical UniversityChongqing Key Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing400016China Chongqing Key Laboratory of Neurobiology Chongqing Medical UniversityChongqing 400016China Department of Anatomy Chongqing Medical UniversityChongqing 400016China Laboratory of Medical Experiment Technology Institute of Life ScienceChongqing Medical UniversityChongqing 400016China Department of Biochemistry and Molecular Biology Chongqing Medical UniversityChongqing 400016China

Osteoporosis(OP)is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk.A novel therapeutic intervention for OP by manipulating cellular autophagy-apoptosis processes to promote skeletal homeostasis is *** effects of the naturally occurring plant extract Liquiritigenin(LG)were demonstrated in an ovariectomy(OvX)-OP mouse model and preosteoblast MC3T3-E1 ***-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy(TEM).The effects of LG on chloroquine(CQ)-and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red,Alizarin red S and alkaline phosphatase(ALP)staining and Western blot *** with LG prevented bone loss,increased osteogenic differentiation in vivo and in vitro,and inhibited osteoclast formation to some *** analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 *** abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome ***,LG stimulates bone growth in Oovx mice through increased osteogenic differentiation and regulation of autophagyapoptosis mechanisms,presenting an auspicious natural therapy for Op.

关键词： Apoptosis Auto-lysosomal degradation Liquiritigenin Osteogenic differentiation Osteoporosis

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Estrogen deficiency exacerbates learning and memory deficits associated with glucose metabolism disorder in APP/PS1 double transgenic female mice

引用

Genes & Diseases 2022年第5期9卷 1315-1331页

作者： Min Luo Qinghua Zeng Kai Jiang Yueyang Zhao zhimin long Yexiang Du Kejian Wang Guiqiong He Chongqing Key Laboratory of Neurobiology Chongqing Medical UniversityChongqing 400016PR China Department of Pathology Suining Municipal Hospital of TCMSuiningSichuan 629000PR China Department of Anatomy Chongqing Medical UniversityChongqing 400016PR China Department of Gastroenterology Suining Central HospitalSuiningSichuan 629000PR China

Alterations in glucose metabolism occur in the brain in the early stage of Alzheimer's disease(AD),and menopausal women have more severe metabolic dysfunction and are more prone to dementia than *** estrogen deficiency-induced changes in glucose metabolism have been previously studied in animal models,their molecular mechanisms in AD remain *** investigate this issue,double transgenic(APP/PS1)female mice were subjected to bilateral ovariectomy at 3 months of age and were sacrificed 1 week,1 month and 3 months after surgery to simulate early,middle and late postmenopause,*** analysis demonstrated that estrogen deficiency exacerbates learning and memory deficits in this mouse model of *** deficiency impairs the function of mitochondria in glucose *** is possible that the occurrence of AD is associated with the aberrant mitochondrial ERβ-mediated IGF-1/IGF-1R/GSK-3βsignaling *** this study,we established a potential mechanism for the increased risk of AD in postmenopausal women and proposed a therapeutic target for AD due to postmenopause.

关键词： Alzheimer’s disease Estrogen deficiency Glucose metabolism disorder GSK-3b IGF-1 Mitochondria

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Dynamic changes of autophagic flux induced by Aβ in the brain of postmortem Alzheimer's disease patients,animal models and cell models

Dynamic changes of autophagic flux induced by Aβ in the bra...

引用

中国解剖学会2021年年会

作者： long zhimin Zhao Yueyang He Guiqiong Institute of Neuroscience Chongqing Medical University Department of Anatomy Chongqing Medical University

Autophagy has been reported to play a dual"double-edged sword"role in the occurrence and development of Alzheimer’s disease (AD).To assess the relationship between AD and autophagy, the dynamic changes of autophagic flux in the brain of postmortem AD patients, animal models and cell models were *** results showed that in AD patients,LC3 was accumulated in large amount,but the expression of Lamp1 and CTSB decreased,and the co-expression of LC3 and CTSB decreased.

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

丙戊酸钠对APP/PS1双转基因小鼠脑内星形胶质细胞和神经营养因子的影响

引用

重庆医科大学学报 2015年第5期40卷 662-665页

作者：龙志敏赵蕾贺桂琼重庆医科大学神经科学中心重庆医科大学基础医学院人体解剖学教研室重庆400016

目的:观察丙戊酸钠(valproic acid sodium salt,VPA)对阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠脑内星形胶质细胞、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)和胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)的影响。方法:取3月龄的APP/PS1双转基因小鼠AD模型小鼠24只,按随机数字表法平均分为治疗组和对照组。VPA治疗组小鼠腹腔注射VPA 30 mg/(kg·d),对照组小鼠腹腔注射等量生理盐水,采用免疫组化学法观察2组小鼠皮质和海马区星形胶质细胞数量的变化,Western blot检测2组小鼠皮质和海马BDNF和GDNF的表达水平。结果:与对照组比较,VPA治疗组小鼠皮质和海马区星形胶质细胞标志物胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)的阳性细胞数量均明显减少(t=5.476、8.793,P均=0.000),BDNF和GDNF表达水平均明显升高(t=4.303,P=0.001;t=2.376,P=0.032)。结论:VPA可抑制星形胶质细胞增生,提高神经营养因子的表达水平。

关键词：阿尔茨海默病丙戊酸钠星形胶质细胞神经营养因子

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

APP/PS1/LC3三转基因小鼠的构建及其自噬流水平研究

引用

重庆医科大学学报 2018年第9期43卷 1140-1146页

作者：陈婧菲贺桂琼龙志敏重庆医科大学神经科学研究中心重庆400016

目的:研究APP/PS1/LC3三转基因小鼠的构建及自噬流情况。方法:将CAG-m RFP-e GFP-LC3转基因自噬流模型小鼠与APP/PS1双转基因阿尔茨海默病(Alzheimer’s Disease,AD)模型小鼠交配繁殖,对产下的子代进行基因分型鉴定,选出同时含有CAG-m R... 详细信息

目的:研究APP/PS1/LC3三转基因小鼠的构建及自噬流情况。方法:将CAG-m RFP-e GFP-LC3转基因自噬流模型小鼠与APP/PS1双转基因阿尔茨海默病(Alzheimer’s Disease,AD)模型小鼠交配繁殖,对产下的子代进行基因分型鉴定,选出同时含有CAG-m RFP-e GFP-LC3基因和APP/PS1的小鼠为APP/PS1/LC3三转基因小鼠,Morris水迷宫实验检测小鼠行为学变化。取6月龄APP/PS1/LC3三转基因小鼠和同窝CAG-m RFP-e GFP-LC3单转基因小鼠各6只,断头取脑后在透射电镜及荧光显微镜下观察自噬流的变化,采用免疫组织化学法检测老年斑的形成,用Western blot检测自噬标志物。结果:基因分型证实APP/PS1/LC3三转基因小鼠构建成功。Morris水迷宫显示,6月龄APP/PS1/LC3三转基因小鼠找到平台的平均潜伏期和路程均明显增加(F=87.096,P=0.000;F=41.583,P=0.000),穿越平台的次数明显减少(2.000±0.707 vs.4.800±0.800,t=2.622,P=0.031)。透射电镜下观察,6月龄APP/PS1/LC3三转基因小鼠脑神经元内出现更多的自噬小泡。荧光显微镜下观察,与同窝CAG-m RFPe GFP-LC3单转基因小鼠比较,6月龄APP/PS1/LC3三转基因小鼠海马区自噬体及自噬溶酶体数量均明显增高(5.894±0.742 vs.14.820±3.350,t=0.017,P=0.000;1.204±0.420 vs.1.840±0.559,t=3.156,P=0.005),大脑皮质内自噬体数量亦明显升高(1.943±0.415 vs.10.030±4.382,t=6.364,P=0.000),但自噬溶酶体数量比较,差异未见统计学意义(0.562±0.207 vs.0.686±0.195,t=0.156,P=0.878)。免疫组化染色结果显6月龄APP/PS1/LC3三转基因大脑皮质及海马区域出现明显老年斑,而同窝CAG-m RFP-e GFP-LC3单转基因小鼠脑内未见老年斑。Western blot结果显示:与同窝CAG-m RFP-e GFP-LC3单转基因小鼠比较,APP/PS1/LC3三转基因小鼠脑内APP蛋白明显升高(0.294±0.070 vs.0.690±0.275,t=3.423,P=0.007),自噬相关蛋白LC3、Beclin1、P62水平均增高(0.241±0.004 vs.0.534±0.019,t=37.170,P=0.000;0.479±0.020 vs.1.180±0.255,t=6.820,P=0.000;0.188±0.007 vs.0.356±0.021,t=18.850,P=0.000),但溶酶体膜蛋白LAMP1表达水平降低(1.450±0.065 vs.0.773±0.043,t=8.705,P=0.000)。结论:APP/PS1/LC3三转基因小鼠自噬被激活,但自噬溶酶体降解受阻,是研究AD自噬流水平的理想动物模型。

关键词：阿尔茨海默病自噬老年斑转基因小鼠

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Dihydroartemisinin ameliorates learning and memory in Alzheimer's disease through promoting autophagosome-lysosome fusion and autolysosomal degradation for Aβclearance

引用

解剖学杂志 2021年第S1期44卷 128-129页

作者： Zhao Yueyang long zhimin Ding Ya Jiang Tingting Liu Jiajun Li Yimin Liu Yuanjie Peng Xuehua Wang Kejian Feng Min He Guiqiong Neuroscience Research Center Chongqing Medical UniversityChongqing 400016China Wuhan Children's Hospital Tongji Medical CollegeHuazhong University of Science&Technology

Dihydroartemisinin(DHA)is the primary active metabolite of Artemisia annua,which is used to treat malaria *** can activate autophagy to remove the harmful or useless su bstances from eukaryotic cells,and maintain the cell viability through autolysosomal degradation *** activation and autophagy flux are playing an important neuroprotective role in the CNS,as they accelerate the removal of toxic protein aggregates intracellularly and extracellularly to prevent Alzheimer's disease(AD).

关键词： Alzheimer protective remove

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Dihydroartemisinin ameliorates learning and memory in Alzheimer's disease through promoting autophagosome-lysosome fusion and autolysosomal degradation for Aβ clearance

Dihydroartemisinin ameliorates learning and memory in Alzhei...

引用

中国解剖学会2021年年会

作者： Zhao Yueyang long zhimin Ding Ya Jiang Tingting Liu Jiajun Li Yimin Liu Yuanjie Peng Xuehua Wang Kejian Feng Min He Guiqiong Neuroscience Research Center Chongqing Medical University Wuhan Children’s Hospital Tongji Medical CollegeHuazhong University of Science & Technology

Dihydroartemisinin (DHA) is the primary active metabolite of Artemisia annua,which is used to treat malaria *** can activate autophagy to remove the harmful or useless substances from eukaryotic cells, and maintain the cell viability through autolysosomal degradation *** activation and autophagy flux are playing an important neuroprotective role in the CNS, as they accelerate the removal of toxic protein aggregates intracellularly and extracellularly to prevent Alzheimer’s disease (AD).

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

去卵巢小鼠股骨微结构的动态变化研究

引用

第三军医大学学报 2021年第17期43卷 1627-1633页

作者：邱宇赵月阳龙志敏汪克建徐凌贺桂琼重庆医科大学附属口腔医院修复科口腔疾病与生物医学重庆市重点实验室重庆市高校市级口腔生物医学工程重点实验室重庆401147 重庆医科大学基础医学院人体解剖学教研室神经科学研究中心重庆400016

目的探究去卵巢骨质疏松小鼠术后不同时期股骨微结构的动态变化。方法8周龄C57雌性小鼠分为去卵巢组(ovariectomy,OVX)和假手术组(sham ovariectomy,Sham),并根据术后不同时间将每组小鼠又分为1周、1个月及3个月组,分别代表绝经早、中... 详细信息

目的探究去卵巢骨质疏松小鼠术后不同时期股骨微结构的动态变化。方法8周龄C57雌性小鼠分为去卵巢组(ovariectomy,OVX)和假手术组(sham ovariectomy,Sham),并根据术后不同时间将每组小鼠又分为1周、1个月及3个月组,分别代表绝经早、中、晚期。称质量后取小鼠股骨进行HE染色、免疫组织化学染色及Micro-CT扫描分析,评估各组股骨远端松质骨、股骨中段皮质骨微结构及成骨相关蛋白水平变化。结果小鼠松质骨形态参数:与Sham组相比,OVX组术后1周骨微结构未见明显破坏,术后1~3个月骨小梁断裂,骨髓腔增大,CT骨参数除***无明显变化外(P>0.05),BV/TV,Tb.N和***均出现显著改变(P0.05)。结论8周龄C57小鼠在OVX术后1周至1个月松质骨微结构明显受损,早于皮质骨变化,可作为骨质疏松病理机制和防治研究的重点阶段。

关键词：骨质疏松骨微结构卵巢摘除术动态变化

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

丙戊酸钠对APP/PS1转基因小鼠自主活动及脑形态结构的影响

引用

第三军医大学学报 2012年第9期34卷 870-873页

作者：陈通龙志敏汪克建赵蕾贺桂琼重庆医科大学基础医学院解剖教研室重庆400016 重庆医科大学基础医学院神经科学研究中心重庆400016

目的研究丙戊酸钠(valproic acid,VPA)对APP/PS1双转基因阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠自主活动及脑组织形态结构的影响,探讨VPA对AD的保护作用及可能机制。方法将3月龄APP/PS1双转基因小鼠及同窝野生型小鼠分为VPA处... 详细信息

目的研究丙戊酸钠(valproic acid,VPA)对APP/PS1双转基因阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠自主活动及脑组织形态结构的影响,探讨VPA对AD的保护作用及可能机制。方法将3月龄APP/PS1双转基因小鼠及同窝野生型小鼠分为VPA处理组和生理盐水对照组,运用VPA[30 mg/(kg.d)]和等量生理盐水腹腔注射4周。旷场实验观察各组小鼠的自主活动能力;尼氏染色、透射电镜观察各组小鼠脑组织的病理改变。结果行为学结果显示:与野生型小鼠相比,AD模型小鼠自主活动明显减少(P0.05);而AD模型小鼠VPA处理组比对照组的自主活动明显减少(P0.05)。电镜结果显示AD模型小鼠对照组脑内神经元细胞核、线粒体及神经毡肿胀明显,突触结构稀松;而AD模型小鼠VPA处理组脑内神经元细胞核、线粒体及神经毡的水肿明显减轻,突触结构清晰。结论 VPA可显著减少APP/PS1双转基因AD模型小鼠的自主行为,显著减轻躁狂症状;VPA可改善APP/PS1双转基因小鼠脑内神经细胞的形态结构,减少肿胀的神经元并抑制神经元数量的减少。

关键词：丙戊酸钠自主活动神经元阿尔茨海默病

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：