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脑康颗粒联合盐酸多奈哌齐对阿尔茨海默病患者的改善作用分析
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作者 陈海生 《医学理论与实践》 2025年第3期413-415,共3页
目的:探讨脑康颗粒联合盐酸多奈哌齐对阿尔茨海默病患者的改善作用。方法:择取2022年8月—2023年8月我院收治的90例阿尔茨海默病患者,用随机数字法分成对照组(n=45)、研究组(n=45)。对照组予盐酸多奈哌齐治疗,研究组在对照组基础上予脑... 目的:探讨脑康颗粒联合盐酸多奈哌齐对阿尔茨海默病患者的改善作用。方法:择取2022年8月—2023年8月我院收治的90例阿尔茨海默病患者,用随机数字法分成对照组(n=45)、研究组(n=45)。对照组予盐酸多奈哌齐治疗,研究组在对照组基础上予脑康颗粒治疗,对比2组疗效、中医症状积分、炎症反应、氧化应激反应和认知功能。结果:研究组临床总有效率、GSH-Px、SOD和MMSE评分均较对照组高,中医症状积分、白介素-1β、TNF-α、白介素-6和MDA均较对照组低,有统计学差异(P<0.05)。结论:脑康颗粒联合盐酸多奈哌齐治疗阿尔茨海默病疗效确切,能减轻炎症及氧化应激损伤,改善认知功能和中医症状积分。 展开更多
关键词 阿尔茨海默病 脑康颗粒 盐酸多奈哌齐 认知功能
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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways 被引量:1
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作者 Biao Xiao Chaoyang Chu +6 位作者 Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li 《Neural Regeneration Research》 SCIE CAS 2025年第9期2706-2726,共21页
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati... A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease. 展开更多
关键词 acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites
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青海高原地区中老年人群闲暇活动与认知障碍的相关研究
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作者 柴长彪 马婧 +4 位作者 汪晓虹 刘建刚 陶宜娟 李鹤 朱爱琴 《中国神经免疫学和神经病学杂志》 2025年第1期42-49,共8页
目的探讨久居高原低氧环境中老年人闲暇活动对认知功能的影响。方法采用横断面方法,选取青海地区(平均海拔<3000 m)509例中老年人,根据简易精神状态量表(mini-mental state examination,MMSE)评分将受试者分为认知障碍组(n=199例)和... 目的探讨久居高原低氧环境中老年人闲暇活动对认知功能的影响。方法采用横断面方法,选取青海地区(平均海拔<3000 m)509例中老年人,根据简易精神状态量表(mini-mental state examination,MMSE)评分将受试者分为认知障碍组(n=199例)和认知正常组(n=310例),将认知障碍组进一步分为轻度认知功能障碍(mild cognitive impairment,MCI)(n=115例)和阿尔茨海默病(Alzheimer disease,AD)组(n=84例)。收集人口学、经济和婚姻状况、慢病史及23项闲暇活动。采用多维度认知和心理量表评估入组者认知功能和神经心理状况。采用Logistic回归分析发生认知障碍的影响因素,Goodman-Kruskal’s Gamma检验分析双向有序变量与认知障碍发生程度的相关性。结果Logistic回归分析显示与配偶同住(OR=0.218)、有氧耐力运动(OR=0.440)、肌肉和耐力运动(OR=0.155)和旅游活动(OR=0.390)是认知障碍的保护因素(P<0.05,P<0.01)。女性(OR=1.833)、年龄(OR=1.085)、体力劳动者以工人和务农(OR=2.613、OR=1.868)是认知障碍的危险因素(均P<0.05)。Gamma相关性分析显示年龄与认知障碍严重程度呈正相关(Gamma=0.456,P<0.01),有氧耐力运动(Gamma=-0.271,P<0.01)、肌肉和耐力运动(Gamma=-0.480,P<0.01)、旅游活动(Gamma=-0.270,P<0.01)频率增加与认知障碍严重程度呈负相关。结论年龄、女性、体力劳动者是导致青海高原地区中老年人认知障碍危险因素;与配偶同住和经常参加有氧耐力运动、肌肉和耐力运动、旅游等闲暇活动可减缓MCI向AD的进展。 展开更多
关键词 高原地区 中老年人群 闲暇活动 轻度认知功能障碍 阿尔茨海默病
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黄芩素对HT22细胞痴呆模型PI3K/Akt信号通路的影响
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作者 叶佳希 朱敏 +1 位作者 陶彦谷 黄启辉 《新中医》 2025年第1期209-216,共8页
目的:观察黄芩素对Aβ_(25-35)诱导的HT22细胞PI3K/Akt信号通路相关因子表达的影响。方法:Aβ_(25-35)40μmol·L^(-1)干预HT22细胞24 h,建立痴呆细胞模型。采用4个不同浓度(5、10、20、40μmol·L^(-1))黄芩素干预痴呆细胞模型... 目的:观察黄芩素对Aβ_(25-35)诱导的HT22细胞PI3K/Akt信号通路相关因子表达的影响。方法:Aβ_(25-35)40μmol·L^(-1)干预HT22细胞24 h,建立痴呆细胞模型。采用4个不同浓度(5、10、20、40μmol·L^(-1))黄芩素干预痴呆细胞模型24 h,CCK-8法检测细胞活力,选取细胞活力最高的黄芩素浓度用于后续实验。实验分为对照组、Aβ_(25-35)组和黄芩素组。流式细胞仪和Hoechest 33342染色检测细胞凋亡情况;JC-10法检测线粒体膜电位情况;DCFH-DA法检测活性氧水平;免疫荧光检测微管相关蛋白轻链3(LC3)蛋白表达情况;Western blot法检测选择性自噬接头蛋白(p62)、自噬关键分子酵母Atg6同系物1(Beclin-1)、磷脂酰肌醇3-激酶(PI3K)、磷酸化磷脂酰肌醇3-激酶(p-PI3K)、丝/苏氨酸蛋白激酶(Akt)、磷酸化丝/苏氨酸蛋白激酶(p-Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)表达。并与PI3K特异性抑制剂LY294002进行比较。结果:最终选择黄芩素浓度10μmol·L^(-1)作为后续实验。与对照组比较,Aβ_(25-35)组细胞凋亡率、ROS水平、p62蛋白表达、mTOR蛋白表达升高(P<0.05),MMP水平、LC3表达、Beclin-1蛋白表达、p-PI3K/PI3K比值、p-Akt/Akt比值降低(P<0.05);与Aβ_(25-35)组比较,黄芩素组细胞凋亡率、ROS水平、p62蛋白表达、mTOR蛋白表达减少(P<0.05),MMP水平、LC3表达、Beclin-1蛋白表达、p-PI3K/PI3K比值、p-Akt/Akt比值升高(P<0.05)。与黄芩素组比较,加入PI3K抑制剂LY294002后,p-PI3K/PI3K、p-Akt/Akt的比值降低,mTOR蛋白表达升高(P<0.05)。结论:黄芩素能够明显改善Aβ_(25-35)诱导的HT22细胞的线粒体功能,减少细胞凋亡和氧化应激,其抗痴呆作用与激活PI3K/AKT信号通路、提高细胞自噬水平有关。 展开更多
关键词 阿尔茨海默病 黄芩素 自噬 线粒体膜电位 氧化应激 细胞凋亡
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The dopaminergic system and Alzheimer's disease
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作者 Yuhan Zhang Yuan Liang Yixue Gu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2495-2512,共18页
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b... Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options. 展开更多
关键词 adverse drug reaction Alzheimer's disease CATECHOLAMINE dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease NEUROTRANSMITTER signaling pathways traditional Chinese medicine TREATMENT
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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression
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作者 Jing Yao Yuan Li +5 位作者 Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song 《Neural Regeneration Research》 SCIE CAS 2025年第7期2068-2083,共16页
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle... Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression. 展开更多
关键词 5′end trimming Alzheimer's disease AMYLOID-BETA amyloid-β-dependent transcription FUBP3 INFLAMMASOME inflammation neuron NLRP3 tau transcription factor
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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance
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作者 Beibei Wu Yuqing Liu +4 位作者 Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng 《Neural Regeneration Research》 SCIE CAS 2025年第3期695-714,共20页
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar... Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease. 展开更多
关键词 ABCA1 Alzheimer's disease AMYLOID-BETA apolipoprotein E cholesterol metabolism LIVER liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid
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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
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作者 Zhimin Long Chuanhua Ge +5 位作者 Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He 《Neural Regeneration Research》 SCIE CAS 2025年第9期2633-2644,共12页
Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal funct... Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,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 disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our 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. 展开更多
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
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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease
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作者 Guibo Qi Han Tang +2 位作者 Jianian Hu Siying Kang Song Qin 《Neural Regeneration Research》 SCIE CAS 2025年第6期1599-1612,共14页
Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. T... Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions. 展开更多
关键词 Alzheimer's disease blood–brain barrier ependymoglial cells HYPOTHALAMUS metabolic diseases neural stem cells NEUROGENESIS neuroinflammatory diseases NEURONS TANYCYTE
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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice
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作者 Yanli Zhang Tian Li +8 位作者 Jie Miao Zhina Zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei Zhang Haiting Li Qiang Su Junhong Guo 《Neural Regeneration Research》 SCIE CAS 2025年第2期533-547,共15页
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A... In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease. 展开更多
关键词 Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1
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Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease
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作者 Hongli Li Jianhua Huang +4 位作者 Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng 《Neural Regeneration Research》 SCIE CAS 2025年第10期2982-2997,共16页
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei... Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies. 展开更多
关键词 Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis
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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease
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作者 Xueyan Liu Wei Wu +8 位作者 Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha 《Neural Regeneration Research》 SCIE CAS 2025年第11期3330-3344,共15页
Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregati... Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease. 展开更多
关键词 Alzheimer's disease amyloid-β ASTROCYTE cognitive impairment D30 dendritic spines GALECTIN-3 MICROGLIA NEUROINFLAMMATION neuron
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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia
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作者 Ying Wang Xiang Zhang +6 位作者 Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li 《Neural Regeneration Research》 SCIE CAS 2025年第3期873-886,共14页
Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o... Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease. 展开更多
关键词 Alzheimer's disease amyloid-β maresin MICROGLIA MONOCYTE NEUROINFLAMMATION resolution RNA-sequencing specialized pro-resolving lipid mediator
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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease
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作者 Yanxin Shen Guimei Zhang +4 位作者 Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun 《Neural Regeneration Research》 SCIE CAS 2025年第3期613-631,共19页
Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid... Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease. 展开更多
关键词 apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder NEUROPROTECTION oxidative stress small-molecule drugs
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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites
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作者 Kirsty Goncalves Stefan Przyborski 《Neural Regeneration Research》 SCIE CAS 2025年第9期2645-2654,共10页
Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is be... Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner. 展开更多
关键词 Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron NOGO Rho A ROCK stem cell three-dimensional culture
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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease
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作者 Qiuquan Cai Lianghui Meng +5 位作者 Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming 《Neural Regeneration Research》 SCIE CAS 2025年第10期2823-2837,共15页
Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the dev... Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods. 展开更多
关键词 Alzheimer’s disease blood-brain barrier DRUGS magnetic resonance imaging-guided focused ultrasound MICROBUBBLES scanning ultrasound ULTRASOUND ultrasound stimulation
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Decoding molecular mechanisms:brain aging and Alzheimer's disease
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作者 Mahnoor Hayat Rafay Ali Syed +9 位作者 Hammad Qaiser Mohammad Uzair Khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir 《Neural Regeneration Research》 SCIE CAS 2025年第8期2279-2299,共21页
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a... The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease. 展开更多
关键词 Alzheimer’s disease brain aging cognitive health DEMENTIA molecular mechanisms neuronal activity NEUROPLASTICITY NEUROTRANSMISSION
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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation
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作者 Yi Ji Chaoyi Yang +7 位作者 Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang 《Neural Regeneration Research》 SCIE CAS 2025年第2期326-342,共17页
Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neur... Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations. 展开更多
关键词 Alzheimer’s disease amyloid deposition apoptotic mechanisms BIOMARKER neural regeneration NEURODEGENERATION repetitive transcranial magnetic stimulation synaptic plasticity
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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease
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作者 Mackenzie M.Spicer Jianqi Yang +5 位作者 Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher 《Neural Regeneration Research》 SCIE CAS 2025年第10期2969-2981,共13页
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode... Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease. 展开更多
关键词 adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus EXERCISE learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)
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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease
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作者 Yinglong Miao Michael S.Wolfe 《Neural Regeneration Research》 SCIE CAS 2025年第1期174-180,共7页
γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the ... γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general. 展开更多
关键词 Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics NOTCH
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