检索结果-南通市图书馆

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

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 therapeuti

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

引用

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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

The mechanism behind activation of the Nod-like receptor family protein 3 inflammasome in Parkinson's disease

引用

Neural Regeneration Research 2022年第4期17卷 898-904页

作者： Jing Wang Xiao-Na Zhang Jin-Ni Fang Fei-Fei Hua Jing-Yang Han Zeng-Qiang Yuan An-Mu Xie Department of Neurology the Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Brain Science Center Academy of Military Medical Sciences of PLABeijingChina

Previous studies have shown that the ATP-P2 X4 receptor signaling pathway mediates the activation of the Nod-like receptor family protein 3(NLRP3)inflammasome.The NLRP3 inflammasome may promote renal interstitial inflammation in diabetic nephropathy.As inflammation also plays an important role in the pathogenesis of Parkinson's disease,we hypothesized that the ATP-P2 X4 receptor signaling pathway may activate the NLRP3 inflammasome in Parkinson's disease.A male rat model of Parkinson's disease was induced by stereotactic injection of 6-hydroxydopamine into the pars compacta of the substantia nigra.The P2 X4 receptor and the NLRP3 inflammasome(interleukin-1βand interleukin-18)were activated.Intracerebroventricular injection of the selective P2 X4 receptor antagonist 5-(3-bromophenyl)-1,3-dihydro-2 H-benzofuro[3,2-e]-1,4-diazepin-2-one(5-BDBD)or knockdown of P2 X4 receptor expression by si RNA inhibited the activation of the NLRP3 inflammasome and alleviated dopaminergic neurodegeneration and neuroinflammation.Our results suggest that the ATP-P2 X4 receptor signaling pathway mediates NLRP3 inflammasome activation,dopaminergic neurodegeneration,and dopamine levels.These findings reveal a novel role of the ATP-P2 X4 axis in the molecular mechanisms underlying Parkinson's disease,thus providing a new target for treatment.This study was approved by the Animal Ethics Committee of Qingdao University,China,on March 5,2015(approval No.QYFYWZLL 26119).

关键词： ATP neurodegenerative disorder neuroinflammation neuroinflammatory response NLRP3 P2X4 Parkinson's disease

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

Chaperone-mediated autophagy and neurodegeneration:connections,mechanisms,and therapeutic implications

引用

Neuroscience Bulletin 2015年第4期31卷 407-415页

作者： Xiaolei Liu Sihua Huang Xingqin Wang Beisha Tang Wenming Li Zixu Mao Department of Neurology Xiangya HospitalCentral South University Department of Pharmacology Emory University School of Medicine Department of Orthopedics the Second Affiliated HospitalMedical School of Xi'an Jiaotong University Department of Neurosurgery Tangdu HospitalFourth Military Medical University Department of Neurology Emory University School of Medicine

Lysosomes degrade dysfunctional intracellular components via three pathways： macroautophagy, microautophagy, and chaperone-mediated autophagy （CMA）. Unlike the other two, CMA degrades cytosolic proteins with a recognized KFERQ-like motif in lysosomes and is important for cellular homeostasis. CMA activity declines with age and is altered in neurodegenerative diseases. Its impairment leads to the accumulation of aggregated proteins, some of which may be directly tied to the pathogenic processes of neurodegenerative diseases. Its induction may accelerate the clearance of pathogenic proteins and promote cell survival, representing a potential therapeutic approach for the treatment of neurodegenerative diseases. In this review, we summarize the current findings on how CMA is involved in neurodegenerative diseases, especially in Parkinson＇s disease.

关键词： autophagy chaperone-mediated autophagy neurodegenerative disorder Parkinson＇s disease risk factors mutant proteins therapeutic target

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

Learning tasks as a possible treatment for DNA lesions induced by oxidative stress in hippocampal neurons

引用

Neural Regeneration Research 2013年第32期8卷 3063-3070页

作者： Dragos Cīrneci Radu Silaghi-Dumitrescu Brain Research Institute Synergon Consulting Faculty of Chemistry and Chemical Engineering Babes-Bolyai University

Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions （8-oxoG） in all organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer＇s dis- ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ- ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair fa- cilitation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effec- tive, it could be the start for designing similar tasks for humans, as a behavioral therapeutic com- plement to the classical drug-based therapy in treating neurodegenerative disorders.

关键词： neural regeneration reviews neurodegenerative disorder reactive oxygen species base excisionrepair cognitive stimulation p300 grants-supported paper neural regeneration

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

Liquid–liquid phase separation in synaptopathies

引用

Neuroprotection 2023年第1期1卷 34-45页

作者： Huihui Jiang Haitao Wu Department of Neurobiology Beijing Institute of Basic Medical SciencesBeijingChina Chinese Institute for Brain Research BeijingChina Key Laboratory of Neuroregeneration Co‐innovation Center of NeuroregenerationNantong UniversityNantongJiangsuChina

Liquid–liquid phase separation has emerged as an important mechanism for regulating cell activity by promoting the formation of membrane-less condensates.In the nervous system,the formation of distinct molecular condensates via phase separation is involved in synaptic assembly and function.Disruption of phase separation is associated with several disease states,such as cancer,neurodegenerative disorders,and neurodevelopmental disorders.This review summarizes the function of phase separation in the assembly and plasticity of the synapse,discusses the role of abnormal phase separation in neurological diseases,and proposes potential treatment options for these neurological diseases based on phase separation.

关键词： neurodegenerative disorder neurodevelopmental disorder phase separation synapse synaptopathy

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

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

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

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：