检索结果-南通市图书馆

Molecular mechanisms of NMDA receptor-mediated excitotoxicity:implications for neuroprotective therapeutics for stroke

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2016年第11期11卷 1752-1753页

作者： Victor Li Yu Tian Wang djavad mowafaghian centre for brain health and department of medicine Vancouver Coastal Health Research InstituteUniversity of British Columbia Vancouver

Excitotoxicity is a process observed in many disease states by which an excessive synaptic excitation causes neuronal death, and is thought to be triggered by the extracellular accumulation of the excitatory neurotransmitter glutamate, which binds and activates ionotropic N-methyl-D-aspartate glutamatergic receptors （NMDARs） in the brain. Normally, NMDARs mediate calcium entry into the cell to regulate physiological processes such as synaptic plasticity and memory,

关键词： NMDAR Molecular mechanisms of NMDA receptor-mediated excitotoxicity

Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2021年第11期16卷 2132-2140页

作者： Tara M.Caffrey Emily B.Button Jerome Robert djavad mowafaghian Center for brain health University of British ColumbiaVancouverBCCanada department of Pathology University of British ColumbiaVancouverBCCanada Institute of Clinical Chemistry University Hospital of ZurichZurichSwitzerland

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and *** supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular *** many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the *** order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular *** towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous *** and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the *** advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential *** innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

关键词： Alzheimer’s disease cerebrovasculature in vitro model neurodegeneration neurovascular unit

Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington＇s Disease

在线全文

学校读者我要写书评

暂无评论

Frontiers in Biology 2016年第6期11卷 439-458页

作者： Kimberly D. Girling Yu Tian Wang djavad Mowafahian centre for brain health & department of medicine University of British Columbia V6T 1Z3 Canada

BACKGROUND： Huntington＇s Disease （HD） is an autosomal dominant neurodegenerative disease causing severe neurodegeneration of the striatum as well as marked cognitive and motor disabilities. Excitotoxicity, caused by overstimulation of NMDA receptors （NMDARs） has been shown to have a key role in the neuropathogenesis of liD, suggesting that targeting NMDAR-dependent signaling may be an effective clinical approach for HD. However, broad NMDAR antagonists are generally poor therapeutics in clinical practice. It has been suggested that GluN2A-containing, synaptically located NMDARs activate cell survival signaling pathways, while GluN2B-containing, primarily extrasynaptic NMDARs trigger cell death signaling. A better approach to development of effective therapeutics for HD may be to target, specifically, the cell-death specific pathways associated with extrasynaptic GluN2B NMDAR activation, while maintaining or potentiating the cell- survival activity of GluN2A-NMDARs. OBJECTIVE： This review outlines the role of NMDAR-mediated excitotoxicity in HD and overviews current efforts to develop better therapeutics for HD where NMDAR excitotoxicity is the target. METHODS： A systematic review process was conducted using the PubMed search engine focusing on research conducted in the past 5-10 years. 235 articles were consulted for the review, with key search terms including ＂Huntington＇s Disease,＂＂excitotoxicity,＂＂NMDAR＂ and ＂therapeutics.＂ RESULTS： A wide range of NMDAR excitotoxicity-based targets for HD were identified and reviewed, including targeting NMDARs directly by blocking GluN2B, extrasynaptic NMDARs and/or potentiating GluN2A, synaptic NMDARs, targeting glutamate release or uptake, or targeting specific downstream cell-death signaling of NMDARs. CONCLUSION： The current review identifies NMDAR-mediated excitotoxicity as a key player in HD pathogenesis and points to various excitotoxicity-focused targets as potential future preventative therapeutics for HD.

关键词： Huntington's Disease NMDA receptor excitotoxicity cell death therapeutics

Placing old wine into new bottles:successful repurposing of bumetanide for treatment of autism spectrum disorder

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science Bulletin 2021年第15期66卷 1491-1492,M0003页

作者： Anthony G.Phillips department of Psychiatry Djavad Mowafaghian Centre for Brain HealthUniversity of British ColumbiaVancouver V6T 1Z4Canada

At a time of unprecedented need and despite significant advances in understanding brain function and related diseases,the drug pipeline for treatment of mental ill-health is failing[1,2].The reasons are many,including the unparalleled complexity of the central nervous system(CNS)itself,a lack of interdisciplinary research collaborations,increased drug development costs,and higher risk of clinical failure of CNS drugs compared with other areas of drug development[3–6].It is now widely recognized that individual dimensions of mental ill health arise from altered neural processes within specific brain circuits that may be shared across diagnostic categories[7,8].The inclusion of cognitive and social processes is particularly appropriate because cognitive dysfunction is of paramount importance to the understanding and treatment of many psychiatric disorders[9].This issue is further compounded by the lack of adequate medication to reverse cognitive and social *** respect to neurodevelopmental disorders that give rise to early onset of a spectrum of symptoms related to schizophrenia,attention deficit hyperactivity disorder,autism spectrum disorders(ASD)to name but a few,the need to discover effective treatment options is particularly urgent.

关键词：自闭症 drugs treatment

N-methyl-D-aspartate glutamate receptors (NMDARs) in stroke pathogenesis and treatments

在线全文

学校读者我要写书评

暂无评论

Journal of Translational Neuroscience 2019年第4期4卷 1-12页

作者： Wenlin Chen Yang Ge Yutian Wang djavad mowafaghian centre for brain health and department of medicine University of British ColumbiaVancouverV6T 2B5Canada

N-methyl-D-aspartate glutamate receptors(NMDARs)play crucial roles in the pathogenesis of neuronal injuries following a stroke insult;therefore,a plethora of preclinical studies focus on better understanding functions of NMDARs and their associated signaling *** the past decades,NMDARs have been found to exert dual effects in neuronal deaths signaling and neuronal survival signaling during cerebral ***,many complex intracellular signaling pathways downstream of NMDAR activation have been elucidated,which provide novel targets for developing much-needed neuro-protectants for patients with *** this review,we will discuss the recent progress in understanding the underlying mechanisms of stroke related to NMDAR activation and the potential therapeutic strategies based on these discoveries.

关键词： N-methyl-D-aspartate glutamate receptors(NMDARs) stroke treatments neuronal survival signaling complex(NSC) neuronal death signaling complex(NDC)

The underlying mechanism of prodromal PD:insights from the parasympathetic nervous system and the olfactory system

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Translational Neurodegeneration 2017年第1期6卷 20-28页

作者： Shu-Ying Liu Piu Chan A.Jon Stoessl department of Neurobiology Neurology and GeriatricsXuanwu Hospital Capital Medical UniversityBeijing 100051China Beijing Key Laboratory on Parkinson’s Disease Parkinson Disease Center of Beijing Institute for Brain DisordersBeijing 100051China Pacific Parkinson’s Research centre Division of Neurology and Djavad Mowafaghian Centre for Brain HealthUniversity of British Columbia and Vancouver Coastal HealthVancouver V6T 1Z3BCCanada

Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical *** stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying *** most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of *** this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the *** review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and ***,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.

关键词： Parkinson’s disease Prodromal Alpha-synuclein Parasympathetic nervous system Olfactory system Subtype

Sexual dimorphism of G protein-coupled receptor signaling in the brain

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第8期19卷 1635-1636页

作者： Sara Aljoudi Hamdan Hamdan Khaled S.Abd-Elrahman department of Physiology and Immunology College of Medicine and Health SciencesKhalifa UniversityAbu DhabiUnited Arab Emirates healthcare Engineering Innovation Center(HEIC) Khalifa UniversityAbu DhabiUnited Arab Emirates department of Anesthesiology Pharmacology and Therapeuticsand Djavad Mowafaghian Center for Brain HealthUniversity of British ColumbiaVancouverBCCanada department of Pharmacology and Therapeutics College of Medicine and Health ScienceKhalifa UniversityAbu DhabiUnited Arab Emirates department of Pharmacology and Toxicology Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by *** and Drug Administration-approved *** of the preclinical research to understand the pharmacology of... 详细信息

关键词： drugs clinical targeted

The role of neuroinfammation in glaucoma

在线全文

学校读者我要写书评

暂无评论

Journal of Translational Neuroscience 2017年第4期2卷 1-11页

作者： Kojic Ljubomir Max S Cynader djavad mowafaghian centre for brain health University of British Columbia Vancouver V6T 1Z4 BC Canada department of Ophthalmology & Visual Sciences University of British Columbia Vancouver V6T 1Z4 BC Canada

Glaucoma is a chronic neurodegener-ative disorder characterized by progressive damage and loss of retinal ganglion cells （RGCs）. It is considered one of the leading causes of irreversible blindness in the older population. There are estimates that glaucoma will affect 80 million individuals worldwide by the end of this de-cade, and yet we are still not able to identify the signals and the mechanisms that trigger this neurodegenerative disease. Various hypotheses have been generated to ad-dress the causes of the progressive RGC death that char-acterizes the disease. Age and increased intraocular pres-sure （IOP） have been established as the main risk factors for the development of glaucoma. Recent studies have identifed additional factors that play a role in the patho-genesis of this complex multifactorial disease, including infammation, oxidative stress, vascular dysregulation, disrupted axonal transport of neurotrophic factors, and the release of neurotoxic agents such as glutamate, nitric oxide and free radicals. The currently approved therapies for glaucoma that seek to reduce IOP, including medica-tions, laser treatment, and surgery, are unable to reliably stop RGC loss and functional impairment. Considering the signifcant personal, medical and socio-economic im-pacts of glaucoma as a leading cause of blindness, there is a pressing need for new innovative treatment strategies. Here we focus on the role of neuroinfammation in glau-coma and the opportunities that new fndings in this area have for the development of future therapeutics.

关键词： glaucoma neuroinfammation immune system complement Toll-like receptors IL-1 TNFα blood retinal barrier metalloproteinases

磷酸化GluN2B亚基在α-syn A53T转基因小鼠黑质中的表达变化

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

青岛大学学报（医学版） 2022年第5期58卷 643-645页

作者：张佳惠刘恒王玉田姜宏青岛大学国家生理学重点(培育)学科山东青岛266071 djavad mowafaghian centre for brain health and department of medicine University of British ColumbiaVancouverBCV6T 2B5Canada

目的研究帕金森病转基因模型小鼠中脑黑质(SN)区磷酸化GluN2B(p-GluN2B)亚基的蛋白含量变化。方法实验所用动物为12~15月龄α-突触核蛋白(α-syn)A53T转基因小鼠和同窝野生型(WT)小鼠。利用开放旷场实验检测小鼠的运动行为能力,采用蛋... 详细信息

目的研究帕金森病转基因模型小鼠中脑黑质(SN)区磷酸化GluN2B(p-GluN2B)亚基的蛋白含量变化。方法实验所用动物为12~15月龄α-突触核蛋白(α-syn)A53T转基因小鼠和同窝野生型(WT)小鼠。利用开放旷场实验检测小鼠的运动行为能力,采用蛋白免疫印迹法检测小鼠SN区p-GluN2B及磷酸化α-syn(pS129α-syn)蛋白表达。结果与WT小鼠相比,α-syn A53T转基因小鼠旷场总运动距离减少(t=2.920,P<0.05),平均运动速度减慢(t=2.518,P<0.05),中脑SN区p-GluN2B和pS129α-syn蛋白表达量明显升高(t=2.470、3.533,P<0.05)。结论α-syn A53T转基因小鼠SN区GluN2B亚基活性增强且可能参与多巴胺能神经元的变性死亡过程。

关键词：帕金森病小鼠,转基因黑质 α突触核蛋白 GluN2B

同方期刊数据库博看期刊