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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijingChina department of neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

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 *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** 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 ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** 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 *** 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.

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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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang department of neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** 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 *** 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 ***,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.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Ischaemic stroke etiological classification system: the agreement analysis of CISS, SPARKLE and TOAST

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Stroke & Vascular neurology 2019年第3期4卷 123-128页

作者： Haojie Zhang Zixiao Li Yunyi Dai Enhui Guo Changqing Zhang Yongjun Wang department of Neurological rehabilitation China Rehabilitation Research CenterBeijingChina department of neurology Beijing Tiantan HospitalBeijingChina department of neurology First People's Hospital of ShangqiuShangqiuChina department of neurology First People's Hospital of Pingdingshan CityPingdingshanChina

Background and purpose The ideal stroke classification system needs to have validity,high reliability and applicability among different stroke research *** Chinese Ischemic Stroke Subclassification(CISS)and the Subtypes of Ischemic Stroke Classification System(SPARKLE)have emerged recently but have not been tested using agreement *** a result,the objective of this study is to investigate the level of agreement among stroke subtype classifications using CISS,SPARKLE and Trial of Org 10172 in Acute Stroke Treatment(TOAST).We also analyse the inter-rater reliability of *** The data include 623 inpatients who have had an ischaemic stroke,accrued from Beijing Tiantan Hospital between 1 October 2015 and 19 April *** to the diagnostic standards of the three subtype classification systems,299 inpatients who satisfied the requirements of our study were independently classified with etiological subtypes,and we compared the three *** There was substantial overall agreement among the three classification systems:CISS versus SPARKLE(kappa value=0.684,p<0.001),CISS versus TOAST(kappa value=0.615,p<0.001)and SPARKLE versus TOAST(kappa value=0.675,p<0.001).The inter-rater reliability of CISS was excellent(kappa value=0.857,p<0.001).Furthermore,among the three subtype classification systems,the variance analysis results of the etiological subtypes were not *** There were generally substantial agreements among three ischaemic stroke etiological classification *** is a valid and reliable classification system,with which different stroke research centres can apply and compare data.

关键词： TOAST system analysis

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Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

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Neural Regeneration Research 2012年第15期7卷 1158-1163页

作者： Jun Zhao Tong Zhang Jianmin Xu Mingli Wang Shengjie Zhao department of neurology China Rehabilitation Research Center School of Rehabilitation Medicine Capital Medical University Beijing100068 China China rehabilitation Research Center Department of Radiology Beijing Boai Hospital Beijing 100068 China

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.

关键词： cerebral stroke constraint-induced movement functional magnetic resonance imaging cerebralfunctional reorganization rehabilitation motor function of upper limbs neural regeneration

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina department of neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients

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Neural Regeneration Research 2016年第11期11卷 1766-1772页

作者： Chao-jin-zi Li Xiao-xia Du Kun Yang Lu-ping Song Peng-kun Li Qiang Wang Rong Sun Xiao-ling Lin Hong-yu Lu Tong Zhang School of rehabilitation Medicine Capital Medical University department of Neurological rehabilitation Beijing Bo'ai HospitalChina Rehabilitation Research Center department of neurology Xi'an Gaoxin Hospital Room of Medical Records Beijing Bo'ai HospitalChina Rehabilitation Research Center

Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the department of Neurological rehabilitation, China rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke （59.6%） was the primary stroke type found in the young group, while ischemic stroke （60.0%） was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction （such as friendship） improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.

关键词： nerve regeneration young stroke patients risk factors recovery of neurological function prognosis Life Satisfaction Questionnaire Barthel Index modified Rank Scale neural regeneration

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Decoding molecular mechanisms:brain aging and Alzheimer's disease

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Neural Regeneration Research 2025年第8期20卷 2279-2299页

作者： Mahnoor Hayat Rafay Ali Syed Hammad Qaiser Mohammad Uzair Khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology(NUST)IslamabadPakistan department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan department of Biological Sciences Faculty of Basic&Applied SciencesInternational Islamic University Islamabad(IIUI)IslamabadPakistan department of Bioengineering King Fahd University of Petroleum and MineralsDhahranSaudi Arabia department of Physiology College of MedicineKing Saud UniversityRiyadhSaudi Arabia department of neurology Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Mental Health Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Biosciences Commission on Science and Technology for Sustainable Development in the South(COMSATS University)IslamabadPakistan department of Psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health Institute of Hebei Medical University ShijiazhuangHebei ProvinceChina department of Neurobiology and Behavior University of CaliforniaIrvineCAUSA Neuroscience Center King Fahad Specialist Hospital DammamDammamSaudi Arabia

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for *** 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 *** these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging *** these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect *** 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.

关键词： Alzheimer’s disease brain aging cognitive health dementia molecular mechanisms neuronal activity neuroplasticity neurotransmission

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Therapeutic Effect of Acupuncture Combining Standard Swallowing Training for Post-stroke Dysphagia:A Prospective Cohort Study

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Chinese Journal of Integrative Medicine 2016年第7期22卷 525-531页

作者：毛立亚李丽丽毛忠南韩艳萍张晓凌姚军孝李明 department of neurology and rehabilitation Affiliated Hospital of Gansu University of Chinese Medicine department of Dermatology Affiliated Hospital of Gansu University of Chinese Medicine department of neurology Affiliated Hospital of Gansu University of Chinese Medicine

Objective： To assess the therapeutic effect of acupuncture combining standard swallowing training for patients with dysphagia after stroke. Methods： A total of 105 consecutively admitted patients with post-stroke dysphagia in the Affiliated Hospital of Gansu University of Chinese Medicine were included： 50 patients from the department of neurology and rehabilitation received standard swallowing training and acupuncture treatment （acupuncture group）; 55 patients from the department of neurology received standard swallowing training only （control group）. Participants in both groups received 5-day therapy per week for a 4-week period. The primary outcome measures included the scores of Videofluoroscopic Swallow Study （VFSS） and the Standardized Swallowing Assessment （SSA）; the secondary outcome measure was the Royal Brisbane Hospital Outcome Measure for Swallowing （RBHOMS）, all of which were assessed before and after the 4-week treatment. Results： A total of 98 subjects completed the study （45 in the acupuncture group and 53 in the control group）. Significant differences were seen in VFSS, SSA and RBHOMS scores in each group after 4-week treatment as compared with before treatment （P〈0.01）. Comparison between the groups after 4-week treatment showed that the VFSS （P=0.007） and SSA scores （P=0.000） were more significantly improved in the acupuncture group than the control group. However, there was no statistical difference （P=0.710） between the acupuncture and the control groups in RBHOMS scores. Conclusions： Acupuncture combined with the standard swallowing training was an effective therapy for post-stroke dysphagia, and acupuncture therapy is worth further investigation in the treatment of post-stroke dysphagia.

关键词： dysphagia stroke acupuncture swallowing training

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Neuroprotective mechanism of TMP269, a selective class ⅡA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2020年第2期15卷 277-284页

作者： Lu Su Dan Liang Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang department of neurology Huashan HospitalFudan UniversityShanghaiChina department of rehabilitation Medicine Huashan HospitalFudan UniversityShanghaiChina

TMP269 is a selective class ⅡA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuroprotective mechanism. Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. The experimental protocol was approved in 2014 by the department of Laboratory Animal Science, Fudan University, China(approval No. 20140143 C001).

关键词： blood-brain barrier drug treatment endothelial cell permeability histone deacetylase inhibitor neuroprotection stroke tissue kallikrein TMP269

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