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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King Department of neurology and Center for Neurodegeneration and experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SO

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Electron beams probe quantum coherence

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Light(Science & Applications) 2024年第4期13卷 596-597页

作者： Nahid Talebi institute for experimental and Applied Physics Kiel University24118 KielGermany

Scientists have traditionally employed superimposed mutually-coherent electron beams for holography and phase retrieval of electron wavepackets.However,recent theoretical exploration delves into the interaction of superposed electron beams with the matter.This investigation aims to elucidate long-range Coulomb correlations and quantum decoherence phenomena when electrons interact with their environment.

关键词： quantum mutually Electron

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Next-generation regenerative therapy for ischemic stroke using peripheral blood mononuclear cells

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Neural Regeneration Research 2024年第11期19卷 2341-2342页

作者： Masato Kanazawa Itaru Ninomiya Yutaka Otsu Masahiro Hatakeyama Department of neurology Brain Research InstituteNiigata UniversityNiigataJapan

Stroke is the second leading cause of death and the third leading cause of disability worldwide after heart disease.Researchers predict that stroke deaths and permanent disabilities will increase worldwide by the year 2050.Single-target therapies may be insufficient,because ischemic cerebral injury involves several mechanisms.Cell-mediated therapies are ideal,because they target multiple cell types to enhance protection and recovery.

关键词： ischemic death cerebral

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Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina institute of experimental neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

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Skull and vertebral bone marrow in central nervous system inflammation

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Fundamental Research 2024年第2期4卷 246-250页

作者： Honglei Ren Qiang Liu Department of neurology Tianjin Neurological InstituteTianjin Institute of ImmunologyState Key Laboratory of Experimental HematologyInternational Joint Laboratory of Ocular DiseasesMinistry of EducationHaihe Laboratory of Cell EcosystemTianjin Medical University General HospitalTianjin 300052China

Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system(CNS).CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory responses.Here,we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS diseases.Further,we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.

关键词： Central nervous system Bone marrow Hematopoiesis Immune cells Neuroinflammation Stroke Multiple sclerosis

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Does HSP27 injection induce glaucoma damage in mice?

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Neural Regeneration Research 2024年第11期19卷 2347-2348页

作者： Stephanie C.Joachim Sabrina Reinehr experimental Eye Research institute University Eye HospitalRuhr-University BochumBochumGermany

In a further aging society,excellent eyesight is an integral part of overall well-being and quality of life.Preserving good vision is crucial to maintaining mobility,independence,and mental health.There can be several reasons for visual impairment in elderly people,these include age-related macular degeneration,the leading cause of vision loss among older adults,cataract,glaucoma,diabetic retinopathy,retinal detachment,and others.

关键词： HSP27 injection damage

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Mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-David M.Gothié Timothy E.Kennedy Department of neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.Myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

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Neural Regeneration Research 2024年第8期19卷 1842-1848页

作者： Lu He Qinming Zhou Chaoyang Xiu Yaping Shao Dingding Shen Huanyu Meng Weidong Le Sheng Chen Department of neurology and institute of neurology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of neurology Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Center for Translational Research on Neurological Diseases the First Affiliated HospitalDalian Medical UniversityDalianLiaoning ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina institute of neurology Sichuan Academy of Medical Sciences-Sichuan Provincial HospitalChengduSichuan ProvinceChina Department of neurology Xinrui HospitalWuxiJiangsu ProvinceChina

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively d

关键词： amyotrophic lateral sclerosis cathelicidin-related antimicrobial peptide hemoglobin label-free quantitative proteomics multi-protein combined diagnostic panel serum biomarkers talin-1 translationally-controlled tumor protein zyxin

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Two become one:combination of two risk factors in a new glaucoma animal model

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Neural Regeneration Research 2024年第5期19卷 982-983页

作者： Nils Kluge Sabrina Reinehr experimental Eye Research institute University Eye HospitalRuhr-University BochumBochumGermany

Glaucoma is a group of eye diseases characterized by progressive loss of retinal ganglion cells(RGCs)and optic nerve degeneration.During this process,the visual field is reduced,and blindness may ultimately occur.Worldwide,glaucoma is the second leading cause of blindness,with about 80 million people affected.Glaucoma is a multifactorial disease and due to its complexity,the exact pathomechanisms are not fully understood yet.However,different risk factors,such as elevated intraocular pressure(IOP),age,or myopia,have been identified to date(EGS,2021).

关键词： elevated exact glaucoma

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Relationship among Parkinson’s disease, constipation, microbes, and microbiological therapy

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World Journal of Gastroenterology 2024年第3期30卷 225-237页

作者： Xin-Yang Yuan Yu-Sen Chen Zhou Liu Department of neurology Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina institute of neurology Guangdong Key Laboratory of Age-Related Cardiac and Cerebral DiseasesZhanjiang 524000Guangdong ProvinceChina

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson’s disease(PD),a prevalent non-motor symptom contributing significantly to patients’morbidity.A marked alteration in the gut microbiota,predominantly an increase in the abundance of Proteobacteria and Bacteroidetes,is observed in PD-related constipation.Conventional treatments,although safe,have failed to effectively alleviate symptoms,thereby necessitating the development of novel therapeutic strategies.Microbiological interventions such as prebiotics,probiotics,and fecal microbiota transplantation(FMT)hold therapeutic potential.While prebiotics improve bowel movements,probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort.FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD.Despite promising developments,the causal relationship between changes in gut microbiota and PD-related constipation remains elusive,highlighting the need for further research in this expanding field.

关键词： Parkinson disease Constipation Gut microbiota Prebiotics Probiotics Fecal microbiota transplantation

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