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Non-linear dynamic state-space network modeling for decoding neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 1879-1880页

作者： Venkata C.Chirumamilla Chi Wang Ip Martin Reich Robert Peach Jens Volkmann Bahman Nasseroleslami Muthuraman Muthuraman Prenatal Pediatrics Institute Children’s National HospitalWashingtonDCUSA Neural Engineering with Signal Analytics and Artificial Intelligence Department of NeurologyUniversity of WürzburgWürzburgGermany academic unit of neurology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Neurodegenerative disorders represent a pervasive global health challenge,yet therapeutic options remain conspicuously *** disorders are inherently dynamic processes within the central nervous system,unfolding across distinct sub-stages:initial structural neuronal alterations(sub-stage 1),functional impairment(sub-stage 2),and culminating in neuronal death(sub-stage 3).

关键词： alterations impairment dynamic

Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla Eng-King Tan Department of neurology National Neuroscience InstituteSingaporeSingapore Neuroscience academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

Treadmill training in Parkinson's disease:possible role of prefrontal modifications in the improved cortical-subcortical network function

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Neural Regeneration Research 2024年第2期19卷 407-408页

作者： Hao Ding Amgad droby Abdul Rauf Anwar Jeffrey M.Hausdorff Bahman Nasseroleslami Anat Mirelman Inbal Maidan Muthuraman Muthuraman Department of neurology University Hospital WürzburgWürzburgGermany academic unit of neurology Trinity College Dublinthe University of DublinDublinIreland Department of neurology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Sagol School of Neuroscience Tel Aviv UniversityTel AvivIsrael Biomedical Engineering Centre UET Lahore(KSK Campus)LahorePakistan Laboratory for Early Markers of Neurodegeneration(LEMON) Center for the Study of MovementCognitionand Mobility(CMCM)Neurological InstituteTel Aviv Sourasky Medical CenterTel AvivIsrael Department of Physical Therapy Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Rush Alzheimer’s Disease Center and Department of Orthopaedic Surgery Rush University Medical CenterChicagoILUSA

Parkinson’s disease(PD)is a complex neurodegenerative disorder characterized by a range of motor symptoms such as bradykinesia,resting tremor,rigidity,and postural instability,as well as non-motor symptoms,such as de... 详细信息

关键词： rigidity fatigue

Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration Research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung Department of neurology Houston Methodist Research InstituteHoustonTXUSA Department of neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

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Neuroscience Bulletin 2024年第4期40卷 500-516页

作者： Wen-Xiang Duan Fen Wang Jun-Yi Liu Chun-Feng Liu Department of neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhou215004China Department of neurology Dushu Lake Hospital affiliated to Soochow UniversitySuzhou215125China Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow UniversitySuzhou215123China

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine *** evidence suggests that gut microbiota and microbial metabolites are involved in the development of *** these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut *** this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor *** research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

关键词： Parkinson’s disease Short-chain fatty acids Microbial metabolites Brain-gut-microbiota axis

The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

Psychogenic non‑epileptic seizures (PNES)in the context of concurrent epilepsy-making the right diagnosis

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Acta Epileptologica 2021年第1期3卷 152-162页

作者： Andreas Liampas Sofia Markoula Panagiotis Zis Markus Reuber Department of neurology Nicosia New General HospitalNicosiaCyprus Department of neurology University Hospital of IoanninaIoanninaGreece Medical School University of CyprusNicosiaCyprus academic neurology unit Royal Hallamshire HospitalUniversity of SheffieldSheffieldUK

Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures(PNES)and comorbid epilepsy is recognized as a comorbidity in about 10–30%of patients with *** combination of epileptic and nonepileptic seizures poses a particular diagnostic *** patients with epilepsy,additional PNES may be suspected on the basis of their typical *** possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment,in patients with frequent emergency admissions with seizures and in those who develop new types of *** description of semiological details by patients and witnesses can suggest additional *** video recordings can support an initial diagnosis,however,especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with *** clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration,fluctuating course,asynchronous movements,pelvic thrusting,side-to-side head or body movement,persistently closed eyes and mouth,ictal crying,recall of ictal experiences and absence of postictal *** can also present as syncope-like episodes with unresponsiveness and reduced muscle *** is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional ***,patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy *** trauma,including sexual abuse,appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES,and the gender imbalance(*** greater prevalence in women)is less marked in patients with PNES and additional epilepsy than those with PNES *** sometimes develop after epilepsy surgery.A

关键词： PNES Epilepsy Risk factors Diagnosis

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu Dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law dr.Neher’s Biophysics Laboratory for Innovative drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina Sichuan Key Medical Laboratory of New drug Discovery and druggability Evaluation Luzhou Key Laboratory of Activity Screening and druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye School and Key Laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu University of TCM ChengduSichuan ProvinceChina School of Basic Medical Sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s *** Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains *** the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first *** Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of *** addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo ***,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was *** importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease *** revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

关键词： Alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae Semen

Causal role of immune cells in obstructive sleep apnea hypopnea syndrome:Mendelian randomization study

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World Journal of Clinical Cases 2024年第7期12卷 1227-1234页

作者： Huang-Hong Zhao Zhen Ma Dong-Sheng Guan Department of Encephalopathy Henan Provincial Hospital of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Personnel The First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of neurology Henan Provincial Hospital of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina

BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic *** immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to *** a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of *** To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical *** A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and *** statistics for each immune cell feature were obtained from the GWAS *** on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic *** results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity *** Following false discovery rate(Fdr)correction,no statistically significant effect of OSAHS on immunophenotypes was ***,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA dr-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.

关键词： Obstructive sleep apnea hypopnea syndrome Immunity Causal inference MR analysis Sensitivity