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Neuro faces of beneficial T cells:essential in brain,impaired in aging and neurological diseases,and activated functionally by neurotransmitters and neuropeptides

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Neural Regeneration Research 2023年第6期18卷 1165-1178页

作者： Mia Levite Faculty of Medicine The Hebrew University of JerusalemCampus Ein KaremJerusalemIsrael Institute of Gene Therapy The Hadassah University Hospital-Ein KaremJerusalemIsrael

T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropept

关键词： aging dopamine glutamate nerve-driven immunity neurological diseases neuropeptides neurotransmitters Personalized Adoptive Neuro-Immunotherapy T cells

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MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases

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Bioactive Materials 2023年第5期23卷 409-437页

作者： Heng Zhou Yan He Wei Xiong Shuili Jing Xingxiang Duan Zhiyun Huang Gurek SNahal Youjian Peng Mingchang Li Yaoqi Zhu Qingsong Ye Center of Regenerative Medicine&Department of Stomatology Renmin Hospital of Wuhan UniversityWuhan430060China Institute of Regenerative and Translational Medicine Tianyou Hospital of Wuhan University of Science and TechnologyWuhanHubei430064China Department of Oral and Maxillofacial Surgery Massachusetts General HospitalHarvard Medical SchoolBoston02114MAUSA School of Dentistry University of QueenslandHerston4006QLDAustralia Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhan430060China Department of Oral and Maxillofacial Surgery Hospital of Taikang Tongji(Wuhan)430050WuhanChina

Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.

关键词： Mesenchymal stem cells Gene delivery neurological diseases Viral vector Nonviral vectors

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Gut microbiota:a new insight into neurological diseases

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Chinese Medical Journal 2023年第11期136卷 1261-1277页

作者： Lanxiang Liu Haiyang Wang Xueyi Chen Peng Xie Department of Neurology Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional diseases The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

In the last decade,it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host.Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases,e.g.,Parkinson’s disease,Alzheimer’s disease,and myasthenia gravis.However,the underlying molecular mechanisms are complex and remain unclear.Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation,indicating that the gut microbiota may be an important regulator of neurological diseases.However,further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases.Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders.In this review,we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases,and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.

关键词： Gut microbiota Gut-brain axis neurological diseases Parkinson’s disease Alzheimer’s disease Autism spectrum disorder Cerebrovascular disease

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Targeting the blood-brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota,circadian rhythms,and their interplays

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4667-4687页

作者： Yanping Wang Weihong Du Xiaoyan Hu Xin Yu Chun Guo Xinchun Jin Wei Wang Department of Neurology the Second Affliated Hospital of Jiaxing CityJiaxing 314000China Beijing Key Laboratory of Cancer Invasion and Metastasis Research Department of Histology and EmbryologySchool of Basic Medical SciencesAdvanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing 100069China Bengbu Medical College(Department of Neurology the Second Hospital of Jiaxing City)Jiaxing 233030China School of Biosciences University of SheffieldSheffeld S102TNUK Department of Physiology and Pathophysiology Capital Medical UniversityBeijing 100069China

AbstracTthe blood-brain barrier(BBB)impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases(AAND).Meanwhile,circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population.Importantly,circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines,resulting in disruption of BBB integrity.Collectively,this provides a new perspective for exploring the relationship among circadian rhythms,gut microbes,and the BBB in aging-accompanied neurological diseases.In this review,we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis,and their potential roles in the BBB disruption that occurs in AAND.Based on existing literature,we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota,which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

关键词： Blood-brain barrier neurological diseases Aging Gut microbiota Circadian rhythms

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The gut microbiome:implications for neurogenesis and neurological diseases

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Neural Regeneration Research 2022年第1期17卷 53-58页

作者： Cheng Liu Shang-Yu Yang Long Wang Fang Zhou Department of Healthcare Administration College of Medical and Health ScienceAsia UniversityTaichungTaiwanChina Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

There is an increasing recognition of the strong links between the gut microbiome and the brain,and there is persuasive evidence that the gut microbiome plays a role in a variety of physiological processes in the central nervous system.This review summarizes findings that gut microbial composition alterations are linked to hippocampal neurogenesis,as well as the possible mechanisms of action;the existing literature suggests that microbiota influence neurogenic processes,which can result in neurological disorders.We consider this evidence from the perspectives of neuroinflammation,microbial-derived metabolites,neurotrophins,and neurotransmitters.Based on the existing research,we propose that the administration of probiotics can normalize the gut microbiome.This could therefore also represent a promising treatment strategy to counteract neurological impairment.

关键词： gut microbiota microbial-derived metabolites microbiota-gut-brain axis neurogenesis neuroinflammation neurological diseases neurotrophins probiotics

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Functional near-infrared spectroscopy in non-invasive neuromodulation

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Neural Regeneration Research 2024年第7期19卷 1517-1522页

作者： Congcong Huo Gongcheng Xu Hui Xie Tiandi Chen Guangjian Shao Jue Wang Wenhao Li Daifa Wang Zengyong Li Beijing Advanced Innovation Center for Biomedical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of EducationSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability National Research Center for Rehabilitation Technical AidsBeijingChina School of Mechatronic Engineering and Automation Foshan UniversityFoshanGuangdong ProvinceChina School of Rehabilitation Engineering Beijing College of Social AdministrationBeijingChina Key Laboratory of Neuro-functional Information and Rehabilitation Engineering of the Ministry of Civil Affairs BeijingChina

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

关键词： brain-computer interface cerebral neural networks functional near-infrared spectroscopy neural circuit neurofeedback neurological diseases neuromodulation non-invasive brain stimulation transcranial electrical stimulation transcranial electrical stimulation

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The role of snapin in regulation of brain homeostasis

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Neural Regeneration Research 2024年第8期19卷 1696-1701页

作者： Jiawen Li Xinqi Huang Yumei An Xueshi Chen Yiyang Chen Mingyuan Xu Haiyan Shan Mingyang Zhang Shanghai Key Lab of Forensic Medicine Key Lab of Forensic ScienceMinistry of JusticeChina(Academy of Forensic Science)ShanghaiChina Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina Department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

关键词： brain homeostasis diabetes neurological diseases snapin traumatic brain injury vesicle fusion

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CRISPR/Cas9 system and its applications in nervous system diseases

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Genes & diseases 2024年第2期11卷 675-686页

作者： Haibin Jiang Mengyan Tang Zidi Xu Yanan Wang Mopu Li Shuyin Zheng Jianghu Zhu Zhenlang Lin Min Zhang The Second School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China The First School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Pediatrics The Second School of MedicineThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China Key Laboratory of Perinatal Medicine of Wenzhou WenzhouZhejiang 325027China Key Laboratory of Structural Malformations in Children of Zhejiang Province WenzhouZhejiang 325000China Zhejiang Provincial Clinical Research Center for Pediatric Disease WenzhouZhejiang 325027China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is an acquired immune system of many bacteria and archaea,comprising CRISPR loci,Cas genes,and its associated proteins.This system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA repair.In recent years,multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological diseases.This article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

关键词： CRISPR/Cas9 Gene editing Mutation neurological diseases Therapeutics

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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian Department of Pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Department of Pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

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The Discrepancy of neurological diseases between China and Western Countries in Recent Two Decades

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Chinese Medical Journal 2018年第8期131卷 886-891页

作者： Jun Ni Fei Han Jing Yuan Han Wang Dong-Chao Shen Yan Xu Li-Ying Cui Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

INTRODUCTION neurological diseases are characterized by high frequency of disability and mortality with pathogenesis largely unknown. Genetic, refractory, and rare diseases account tbr a large proportion of neurological diseases： sympathetically, limited curable treatments are available. Hundreds of millions of people worldwide are affected by neurological disorders. The diagnosis and treatment of neurological disorders have made significant progress in recent years, especially in the past two decades with the rapid development of technology.

关键词： Discrepancy Progression neurological diseases China Western

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