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Presence of antibodies against low-density lipoprotein receptor-related protein 4 and impairment of neuromuscular junction in a Chinese cohort of amyotrophic lateral sclerosis
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作者 Lin Lei Xin-Ming Shen +8 位作者 Shu-Yan Wang Yan Lu Suo-Bin Wang Hai Chen Zheng Liu Ya-Sheng Ouyang Jian-Ying Duo Yu-Wei Da Zhi-Guo Chen 《中华医学杂志:英文版》 SCIE CAS CSCD 2019年第12期1487-1489,共3页
Amyotrophic lateral sclerosis (ALS) is a heterogeneous disorder characterized by a loss of upper and lower motor neurons with neither clear pathogenesis nor effective treatment. Thus, potential biomarkers are needed t... Amyotrophic lateral sclerosis (ALS) is a heterogeneous disorder characterized by a loss of upper and lower motor neurons with neither clear pathogenesis nor effective treatment. Thus, potential biomarkers are needed to classify the disease and find new drug targets. Previous studies have shown that auto-antibodies against the low-density lipoprotein receptor-related protein 4 (LRP4), called the anti-LRP4 antibodies, are found in ~23% patients of Greek and Italian ALS cohorts,[1] and in 10% of the American ALS population.[2] Anti-LRP4 antibodies were previously identified in myasthenia gravis (MG), the most common neuromuscular junction (NMJ) disorder, and were shown to cause NMJ abnormality in animal studies.[3] Here, we studied anti-LRP4 antibodies in Chinese patients and investigated the correlation between anti-LRP4 antibodies and abnormal neuromuscular transmission in ALS. 展开更多
关键词 ANTIBODIES AGAINST amyotrophic lateral SCLEROSIS NEUROMUSCULAR junction
Protective effect of hydrogen sulfide on oxidative stress-induced neurodegenerative diseases 预览
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作者 Rubaiya Tabassum Na Young Jeong Junyang Jung 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期232-241,共10页
Hydrogen sulfide is an antioxidant molecule that has a wide range of biological effects against oxidative stress. Balanced oxidative stress is also vital for maintaining cellular function in biological system, where r... Hydrogen sulfide is an antioxidant molecule that has a wide range of biological effects against oxidative stress. Balanced oxidative stress is also vital for maintaining cellular function in biological system, where reactive oxygen species are the main source of oxidative stress. When the normal redox balance is disturbed, deoxyribonucleic acid, lipid, and protein molecules are oxidized under pathological conditions, like diabetes mellitus that leads to diabetic peripheral neuropathy. In diabetes mellitus-induced diabetic peripheral neuropathy, due to hyperglycemia, pancreatic beta cell(β cell) shows resistance to insulin secretion. As a consequence, glucose metabolism is disturbed in neuronal cells which are distracted from providing proper cell signaling pathway. Not only diabetic peripheral neuropathy but also other central damages occur in brain neuropathy. Neurological studies regarding type 1 diabetes mellitus patients with Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis have shown changes in the central nervous system because high blood glucose levels(HbA1 c) appeared with poor cognitive function. Oxidative stress plays a role in inhibiting insulin signaling that is necessary for brain function. Hydrogen sulfide exhibits antioxidant effects against oxidative stress, where cystathionine β synthase, cystathionine γ lyase, and 3-mercaptopyruvate sulfurtransferase are the endogenous sources of hydrogen sulfide. This review is to explore the pathogenesis of diabetes mellitus-induced diabetic peripheral neuropathy and other neurological comorbid disorders under the oxidative stress condition and the anti-oxidative effects of hydrogen sulfide. 展开更多
关键词 Alzheimer's DISEASE amyotrophic lateral SCLEROSIS antioxidant diabetic peripheral NEUROPATHY DNA oxidation hydrogen SULFIDE mitochondrial dysfunction oxidative stress Parkinson's DISEASE reactive oxygen species
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Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis
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作者 Qiong-Hua Sun Yan-Ran Li +3 位作者 Wen-Jie Lan Fei Yang Fang Cui Xu-Sheng Huang 《中华医学杂志:英文版》 SCIE CAS CSCD 2019年第9期1023-1027,共5页
Background:It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage.The time taken for symptoms to spread from spinal or bulbar regions to both (time to ... Background:It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage.The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization;TTG) is considered a strong predictor of survival;however,this has rarely been studied in Asian populations.The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS,with a focus on the association between TTG and overall survival.Methods:Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017.Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models.The clinical data of the patients were recorded and analyzed.Variables studied were age at symptom onset,sex,site of symptom onset,diagnostic latency,TTG,diagnostic category,ALS Functional Rating Scale-revised score,percent predicted forced vital capacity (FVC%),and disease progression rate (DPR) at diagnosis.Results:The mean age at onset was 54 (SD = 10.2) years,and the median survival time from symptom onset was 41 months (95% confidence interval:34–47).By univariate analysis,factors independently affecting survival were age at symptom onset (Log rank = 15.652,P<0.0001),TTG (Log rank = 14.728,P<0.0001),diagnostic latency (Log rank = 11.997,P = 0.001),and DPR (Log rank = 6.50,P = 0.011).In the Cox multivariate model,TTG had the strongest impact on survival time (hazard ratio = 0.926,P = 0.01).Conclusions:TTG can be used as an effective indicator of prognosis in patients with sporadic ALS. 展开更多
关键词 Amyotrophic LATERAL SCLEROSIS Time to generalisation (TTG) Prognosis Survival
Fungal-contaminated grass and well water and sporadic amyotrophic lateral sclerosis 预览
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作者 Peter William French Russell Ian Ludowyke Gilles J.Guillemin 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1490-1493,共4页
Fungi are important infectious disease-causing agents,but are often overlooked as environmental factors in disease.We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic la... Fungi are important infectious disease-causing agents,but are often overlooked as environmental factors in disease.We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis(ALS),the most common form of motor neurone disease.Approximately 90%cases of ALS are sporadic,and the aetiology of sporadic ALS is still unknown.We have previously postulated that grass or soil-associated fungal infections may be a leading cause of sporadic ALS.Herein we extend this proposal to water-associated fungi.A wide variety of fungi have been reported in drinking water including Acremonium,Alternaria,Aspergillus,Cladosporium,Fusarium,Penicillium and Trichoderma.Some of these are known to produce neurotoxic mycotoxins.Despite this,drinking water is not routinely monitored for fungal contamination.Fungal contamination could explain the close correlation between distribution of well water and cases of sporadic ALS in the United States.We propose several mechanisms by which an opportunistic fungal infection from environmental exposure(to water,soil or plants)can lead to long term neuronal degradation resulting in the hallmarks of ALS.If confirmed,the association between fungal infection and sporadic ALS could lead to novel treatment strategies for this progressive and fatal disease. 展开更多
关键词 amyotrophic lateral SCLEROSIS FUNGI motor neurone disease mycotoxins NEUROTOXINS ALS well water SPORADIC ALS
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Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis:pre-clinical evidence and potential for clinical application 预览
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作者 Chandler L.Walker 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1522-1524,共3页
Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that causes death of upper and lower motor neurons(MNs)in the central nervous system(CNS).The disease afflicts most people in pr... Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that causes death of upper and lower motor neurons(MNs)in the central nervous system(CNS).The disease afflicts most people in prime periods of productivity in life,and it is estimated approximately 200,000 individuals in the United States live with ALS and any given time.Though a significant percentage of individuals with ALS have a genetic or hereditary form of the disease,the majority are sporadic cases with unknown etiologies.Regardless of cause,onset and progression of the disease is similar in all ALS patients,with minor initial outward symptoms followed by rapid deterioration of motor function leading to widespread paralysis,respiratory dysfunction and death.Despite the distressing and debilitating nature of ALS,no cures and limited potential treatment options exist.Therefore,identifying targets for effective therapy leading to delayed disease progression,increased quality of life,and extended lifespan are critical areas of investigation.In addition,identifying biomarkers of disease progression is incredibly important as diagnosis often occurs once the disease is in late stages and lifespan is only an average of 3–5 years after diagnosis.As the cellular and physiological processes known to influence or be involved in ALS are numerous,the complexity of the disease is a major detriment in developing effective therapies.Aside from the ubiquitous death of MNs,inflammatory and immunologic response in the spinal cord,brain and target muscles,and signal pathway changes that precede or are induced by MN death have been identified at multiple stages of disease progression. 展开更多
关键词 Amyotrophic LATERAL devastating PROGRESSIVE NEURODEGENERATIVE disease PROGRESSION
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Transcriptional dysregulation in neurodegenerative diseases:who tipped the balance of Yin Yang 1 in the brain? 预览
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作者 Zhefan Stephen Chen Ho Yin Edwin Chan 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第7期1148-1151,共4页
Yin Yang 1(YY1)is a multi-functional transcription factor that regulates gene expression in a range of cell types,including neurons.It controls neuronal differentiation,as well as neuronal specification and migration ... Yin Yang 1(YY1)is a multi-functional transcription factor that regulates gene expression in a range of cell types,including neurons.It controls neuronal differentiation,as well as neuronal specification and migration during the development of the mammalian nervous system.Besides,YY1 also mediates the transcription of genes that are required for neuronal survival.An impairment of the transcriptional function of YY1 causes neuronal death.This review summarizes recent research findings that unveil the dysfunction of YY1 in multiple neurodegenerative disorders.The expression of disease proteins perturbs the function of YY1 via distinct molecular mechanisms,including recruitment to protein aggregates,protein degradation and aberrant nuclear/cytoplasmic shuttling.Understanding the pathogenic roles of YY1 will further broaden our knowledge of the disease mechanisms in distinct neurodegenerative disorders. 展开更多
关键词 Alzheimer’s disease amyotrophic lateral SCLEROSIS neurodegeneration PROTEIN aggregates recruitment PROTEIN degradation SUBCELLULAR localization TRANSCRIPTIONAL regulation YIN Yang 1
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Genetic targeting of astrocytes to combat neurodegenerative disease 预览
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作者 Rachel Kéry Allen P. F. Chen Gregory W. Kirschen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期199-211,共13页
Astrocytes, glial cells that interact extensively with neurons and other support cells throughout the central nervous system, have recently come under the spotlight for their potential contribution to, or potential re... Astrocytes, glial cells that interact extensively with neurons and other support cells throughout the central nervous system, have recently come under the spotlight for their potential contribution to, or potential regenerative role in a host of neurodegenerative disorders. It is becoming increasingly clear that astrocytes, in concert with microglial cells, activate intrinsic immunological pathways in the setting of neurodegenerative injury, although the direct and indirect consequences of such activation are still largely unknown. We review the current literature on the astrocyte’s role in several neurodegenerative diseases, as well as highlighting recent advances in genetic manipulation of astrocytes that may prove critical to modulating their response to neurological injury, potentially combatting neurodegenerative damage. 展开更多
关键词 Alzheimer's DISEASE amyotrophic lateral SCLEROSIS GLIA immune system inflammation Parkinson's DISEASE reactive ASTROCYTE regeneration
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Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis
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作者 Li-Lan Fu He-Xiang Yin +1 位作者 Ming-Sheng Liu Li-Ying Cui 《中华医学杂志:英文版》 SCIE CAS CSCD 2019年第5期542-550,共9页
Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower neurons with no effective cure. Electrophysiological studies have found decremental responses d... Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. Methods: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1,2012 and February 28,2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. Results: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1%(46/85) in the ALS group, and the results of different nerves were 54.1 %(46/85) of the accessory nerve, 8.2%(7/85) of the ulnar nerve and 0%(0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100%(41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. Conclusions: Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases. 展开更多
关键词 Amyotrophic lateral SCLEROSIS Generalized MYASTHENIA GRAVIS NEUROMUSCULAR junction REPETITIVE nerve stimulation
Characteristics and advantages of adenoassociated virus vector-mediated gene therapy for neurodegenerative diseases 预览
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作者 Yuan Qu Yi Liu +2 位作者 Ahmed Fayyaz Noor Johnathan Tran Rui Li 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期931-938,共8页
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons,even leading to the permanent loss of function.Gene therapy via gene replacement or ge... Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons,even leading to the permanent loss of function.Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients.Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system.This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system.Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration. 展开更多
关键词 nerve REGENERATION central nervous system gene therapy NEURODEGENERATIVE DISEASE viral vector ADENO-ASSOCIATED virus Alzheimer’s DISEASE Parkinson’s DISEASE Huntington’s DISEASE amyotrophic lateral SCLEROSIS spinal muscular atrophy neural REGENERATION
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Lessons from glaucoma:rethinking the fluid-brain barriers in common neurodegenerative disorders 预览
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作者 Francisco Javier Carreras 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期962-966,共5页
Glaucoma has been recently characterized as a member of the group of anoikis-related diseases.Anoikis,a form of apoptosis,can be triggered by the unfastening of adherent junctions present in astrocytes.In those areas ... Glaucoma has been recently characterized as a member of the group of anoikis-related diseases.Anoikis,a form of apoptosis,can be triggered by the unfastening of adherent junctions present in astrocytes.In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes,a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves.In glaucoma,the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head.The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes.As the cerebrospinal fluid has a similar base calcium concentration,a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons.Here the similitude between glaucoma,amyotrophic lateral sclerosis and Alzheimer’s disease are discussed and the concept of the break in the fluid-brain barrier,as an event separated from the blood-brain barrier,is stressed. 展开更多
关键词 fluid-brain barriers blood-brain barrier CEREBROSPINAL FLUID aqueous humor calcium ion GLAUCOMA amyotrophic lateral SCLEROSIS Alzheimer’s disease
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Strategies to promote the maturation of ALS-associated SOD1 mutants:small molecules return to the fold 预览
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作者 Luke McAlary Justin J.Yerbury 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1511-1512,共2页
(Cu)^IIATSM(CuATSM)promotes the proper folding of familial amyotrophic lateral sclerosis(fALS)-associated copper,zinc superoxide dismutase(SOD1):ALS is a progressive neurodegenerative disease that affects motor neuron... (Cu)^IIATSM(CuATSM)promotes the proper folding of familial amyotrophic lateral sclerosis(fALS)-associated copper,zinc superoxide dismutase(SOD1):ALS is a progressive neurodegenerative disease that affects motor neurons in the cortex and spinal cord,resulting in paralysis and ultimately death.The majority of cases are sporadic and the remainder are fALS where a subset of cases are associated with over 160,mostly missense,mutations in the SOD1 enzyme structure.Generally,these mutations impede the correct folding of SOD1 by disrupting either metal binding,disulfide formation,and/or dimerization,leading to the accumulation of misfolded SOD1 which can form the intracellular inclusions observed in patient tissue. 展开更多
关键词 (Cu)^IIATSM(CuATSM) FAMILIAL amyotrophic patient tissue
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Mitophagy links oxidative stress conditions and neurodegenerative diseases 预览
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作者 Ulfuara Shefa Na Young Jeong +4 位作者 In Ok Song Hyung-Joo Chung Dokyoung Kim Junyang Jung Youngbuhm Huh 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第5期749-756,共8页
Mitophagy is activated by a number of stimuli,including hypoxia,energy stress,and increased oxidative phosphorylation activity.Mitophagy is associated with oxidative stress conditions and central neurodegenerative dis... Mitophagy is activated by a number of stimuli,including hypoxia,energy stress,and increased oxidative phosphorylation activity.Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases.Proper regulation of mitophagy is crucial for maintaining homeostasis;conversely,inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species,including reactive oxygen species and reactive nitrogen species,resulting in various neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and amyotrophic lateral sclerosis.These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species.As mitophagy is essential for normal body function,by targeting mitophagic pathways we can improve these disease conditions.The search for effective remedies to treat these disease conditions is an ongoing process,which is why more studies are needed.Additionally,more relevant studies could help establish therapeutic conditions,which are currently in high demand.In this review,we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration.We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases. 展开更多
关键词 nerve regeneration MITOPHAGY central nervous system Alzheimer’s DISEASE Parkinson’s DISEASE Huntington’s DISEASE amyotrophic lateral SCLEROSIS oxidative SPECIES REACTIVE oxygen SPECIES REACTIVE nitrogen SPECIES
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Amyotrophic lateral sclerosis: a complex syndrome that needs an integrated research approach 预览
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作者 Javier Riancho Francisco J. Gil-Bea +1 位作者 Ana Santurtun Adolfo López de Munaín 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第2期193-196,共4页
Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related t... Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. However, the translation into clinical practice has been largely unsuccessful and the compounds failed when were tested in clinical trials. This might be explained, at least partially, by the enormous complexity of the disease both from clinico-epidemiological and a pathogenic points of view. In this review, we will briefly comment on the complexity of the disease focusing on some recent findings, and we will suggest how amyotrophic lateral sclerosis research might be reoriented to foster the advance in the diagnostic and therapeutic questions. 展开更多
关键词 amyotrophic LATERAL SCLEROSIS ALS environment EPIDEMIOLOGY GENES PHENOTYPE therapy
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Oxidative stress: the lowest common denominator of multiple diseases 预览
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作者 Veronika Matschke Carsten Theiss Johann Matschke 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第2期238-241,共4页
Oxygen is essential to the human life and life of all aerobic organisms.The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life ... Oxygen is essential to the human life and life of all aerobic organisms.The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms.However,cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source.Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis.When the concentration of free radicals exceeds a critical level and homeostasis is disturbed,oxidative stress occurs leading to damage of multiple cellular molecules and compartments.Therefore,oxidative stress plays an important role in the physiology and pathology of various diseases.Often,the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases,leading to functional losses of the organism,as in the case of amyotrophic lateral sclerosis,or cells develop metabolic mechanisms to use this system as protection against external influences,such as in the case of glioblastoma cells.Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases.Thus,regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate,the focus should be on the oxidative protection system. 展开更多
关键词 NEURODEGENERATIVE disease amyotrophic LATERAL SCLEROSIS cancer GLIOBLASTOMA REACTIVE oxygen species metabolism ANTIOXIDANT protection system
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Safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateralsclerosis therapy 预览
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作者 Monika Barczewska Mariusz Grudniak +5 位作者 Stanislaw Maksymowicz Tomasz Siwek Tomasz Oldak Katarzyna Jezierska-Wozniak Dominika Gladysz Wojciech Maksymowicz 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第2期313-318,共6页
Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have b... Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have been shown to exhibit prospects in the treatment of amyotrophic lateral sclerosis. However, the safety of their clinical application needs to be validated. To investigate the safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy, 43 patients (16 females and 27 males, mean age of 57.3 years) received an average dose of 0.42 × 106 cells/kg through intrathecal administration at the cervical, thoracic or lumbar region depending on the clinical symptoms. There was a 2 month interval between two injections. The adverse events occurring during a 6-month treatment period were evaluated. No adverse events occurred. Headache occurred in one case only after first injection of stem cells. This suggests that intrathecal injection of Wharton's Jelly-derived mesenchymal stem cells is well tolerated in patients with amyotrophic lateral sclerosis. This study was approved by the Bioethical Committee of School of Medicine, University of Warmia and Mazury in Olsztyn, Poland (approval No. 36/2014 and approval No. 8/2016). This study was registered with the ClinicalTrials.gov (identifier: NCT02881476) on August 29, 2016. 展开更多
关键词 amyotrophic lateral sclerosis STEM CELLS THERAPY intrathecal injections Wharton's jelly-derived mesenchymal STEM CELLS adverse events safety cerebrospinal fluid neural regeneration
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Unique characteristics of the genetics epidemiology of amyotrophic lateral sclerosis in China
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作者 Qianqian Wei Xueping Chen +5 位作者 Yongping Chen Ruwei Ou Bei Cao Yanbing Hou Lingyu Zhang Hui-Fang Shang 《中国科学:生命科学英文版》 SCIE CAS CSCD 2019年第4期517-525,共9页
Continual discoveries of new genes and unraveling the genetic etiology in amyotrophic lateral sclerosis(ALS)have provided greater insight into the underlying pathogenesis in motor neuron degeneration,as well as facili... Continual discoveries of new genes and unraveling the genetic etiology in amyotrophic lateral sclerosis(ALS)have provided greater insight into the underlying pathogenesis in motor neuron degeneration,as well as facilitating the disease modeling and the testing of targeted therapeutics.While,the genetic etiology accounted for two-thirds of FALS and approximately 11% of SALS in Caucasians.However,the contributions of these causative genes to ALS vary among different populations.Furthermore,the prominent difference between Chinese population and other ethnics remains a source of ongoing debate.We systemically reviewed genetics literature of Chinese ALS populations and updated the mutation frequencies of the main ALS-implicated genes aiming to determine the genetic features of ALS in Chinese population.We also reviewed the associations between ALSimplicated single nucleotide polymorphisms(SNPs)and the risk of ALS in Chinese population.A total of 116 studies were included in this analysis(86 gene mutation study articles and 30 SNPs study articles).The results showed that the overall gene mutation rates of ALS-related causative genes were 55.0% in familial ALS(FALS)and 11.7% in sporadic ALS(SALS)in Chinese population.In Chinese FALS,the highest mutation frequency was found in SOD1 gene(25.6%),followed by FUS(5.8%),TARDBP(5.8%),DCTN1(3.6%)and C9 orf 72(3.5%).In Chinese SALS,the highest mutation frequency was also identified in SOD1 gene(1.6%),followed by ANXA11(1.4%),FUS(1.3%),SQSTM1(1.0%),OPTN(0.9%)and CCNF(0.8%).The associations between several SNPs and risk of ALS were also reported in Chinese population.The genetic features of ALS in Chinese population are significantly different from those in Caucasian population,indicating an association between genetic susceptibility and origin of population.Further explorations are required to understand the gene complexity of ALS,including the contribution of most minor genes and the molecular mechanisms in ALS pathologies. 展开更多
关键词 amyotrophic LATERAL SCLEROSIS gene mutation single NUCLEOTIDE POLYMORPHISMS
Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study
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作者 Dong-Chao Shen Yin-Yan Xu +7 位作者 Bo Hou Hong-Fei Tai Kang Zhang Shuang-Wu Liu Zhi-Li Wang Feng Feng Ming-Sheng Liu Li-Ying Cui 《中华医学杂志:英文版》 SCIE CAS CSCD 2018年第24期2904-2909,共6页
Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonan... Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry;cerebral blood flow (CBF) evaluated by arterial spin labeling;functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI;and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion: Multimodal MRI could be used to monitor short-term brain changes in ALS patients. 展开更多
关键词 Amyotrophic Lateral SCLEROSIS Disease PROGRESSION MONITORING VALUE MULTIMODAL Magnetic Resonance Imaging
The role of ubiquitinated TDP-43 in amyotrophiclateral sclerosis
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作者 Yi Dong Yan Chen 《神经免疫与神经炎症(英文版)》 2018年第2期8-17,共10页
Deposition of intracellular ubiquitin inclusion in motor neurons is one of the leading pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). The transactive response DNA binding protein-43 (TDP-43) is the main... Deposition of intracellular ubiquitin inclusion in motor neurons is one of the leading pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). The transactive response DNA binding protein-43 (TDP-43) is the main component of intracellular ubiquitin inclusion bodies in pathological deposits. TDP-43 is mainly distributed in the nucleus of neurons, and participates in nuclear RNA transcription, alternative splicing and mRNA stability regulation. The tardbp, as a coding gene, provides instructions for making TDP-43. After post-translational modification, the pathological TDP-43 induces pathological deposition in cells and is associated with neurodegenerative diseases, which is similar to tau in Alzheimer's disease and alpha-synuclein in Parkinson's disease. The pathogenic tardbp mutation can affect the localization of reverse transcription in the cell. This review summarizes the mechanisms underlying the pathogenesis of ALS by ubiquitination of TDP-43 protein. 展开更多
关键词 TDP-43 PROTEIN UBIQUITINATION TARDBP amyotrophic LATERAL SCLEROSIS
Gray Matter Volume Changes over the Whole Brain in the Bulbar-and Spinal-onset Amyotrophic Lateral Sclerosis:a Voxel-based Morphometry Study 预览
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作者 Zhiye Chen Mengqi Liu Lin Ma 《中国医学科学杂志:英文版》 CAS CSCD 2018年第1期20-28,共9页
To investigate cerebral structural signatures of the bulbar-and spinal-onset amyotrophic lateral sclerosis(ALS)using voxel-based morphometry on magnetic resonance imaging.Methods The MR structural images of the brain ... To investigate cerebral structural signatures of the bulbar-and spinal-onset amyotrophic lateral sclerosis(ALS)using voxel-based morphometry on magnetic resonance imaging.Methods The MR structural images of the brain were obtained from 65 ALS patients(15 bulbar-onset,50 spinalonset)and 65 normal controls(NC)on a 3.0T MRI system.Gray matter(GM)volume changes were investigated by voxel-based morphometry,and the distribution of the brain regions with volume changes was compared between ALS and normal controls,as well as between bulbar-onset and spinal-onset ALS based on Neuromorphometrics atlas.Results On voxel-level the decreased volume of brain regions in ALS patients was located in the right precentral gyrus(rPrcGy)and right middle frontal gyrus compared with that in NC.The bulbar-onset ALS presented extramotor cortex atrophy(fronto-temporal pattern),including left medial orbital gyrus,left inferior temporal gyrus and right middle temporal gyrus;the spinal-onset ALS suffered from motor cortex atrophy(rPrcGy dominance)and extra-motor cortex atrophy(fronto-temporal and extra-fronto-temporal pattern)compared with NC.The spinal-onset ALS featured by GM volume loss of left postcentral gyrus and bulbar-onset ALS featured by GM volume loss of left middle temporal gyrus compared with each other.Conclusions The asymmetric GM atrophy of the motor cortex and extra-motor cortex represents the common MRI structural signatures of spinal-onset ALS,and sole extra-motor cortex atrophy represents the structural signatures of bulbar-onset ALS.The present study also demonstrated that the pattern of GM damage is likely to distribute wider in spinal-onset ALS than in bulbar-onset ALS. 展开更多
关键词 amyotrophic lateral SCLEROSIS GRAY matter magnetic resonance imaging precentral GYRUS voxel-based MORPHOMETRY
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How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis?
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作者 Jian-Feng Liu Ou-Xiang Zheng +2 位作者 Jun-Guo Xin Hannah HChen John JXin 《神经免疫与神经炎症(英文版)》 2017年第6期109-116,共8页
Abnormal immune response/inflammation is present in patients of amyotrophic lateral sclerosis (ALS). Autoimmune-related inflammation has been thought to be involved in the pathogenesis of ALS. However, how the abnorma... Abnormal immune response/inflammation is present in patients of amyotrophic lateral sclerosis (ALS). Autoimmune-related inflammation has been thought to be involved in the pathogenesis of ALS. However, how the abnormal immune responses are initiated, what specific immune cells and how these immune cells are involved in this disease have not been well understood. This is partly owing to two facts of ALS: late diagnosis and chronic nature. The late diagnosis makes it difficult to conclude whether the abnormal immune responses/inflammation is the cause or result of the disease. The chronic nature makes it difficult to determine the best timing for the detection of such autoimmune responses. To resolve these two challenges for research, the authors introduced motor nerve injury (facial nerve axotomy, FNA) into a pre-symptomatic mouse ALS model (8-week-old SOD1G93A mice), which induces a readily detectable immune response in a predictable time period (3-14 days). The authors found that pre-symptomatic SOD1G93A mice showed a higher basal level of T cell activation and Th17 cells than WT mice, which can be further increased by FNA. However, why these pro-inflammatory Th lymphocyte subsets are preferentially elicited in ALS has been elusive. Recently, several studies support that the programmed necrosis (necroptosis), a new type of cell death, is present in ALS. Because necroptosis results in the release of pro-inflammatory stimuli, we speculate that initial motoneuron (MN) necroptosis may be the cause of abnormal immune responses in the development of ALS, and subsequently, inflammation/immune response serve as an amplifier to cause more MN death. Here, the authors reviewed recent studies concerning the type of MN death, the inflammation/immune responses and the research strategies for ALS. With the available evidences from the literature, the authors present a hypothesized working model to indicate the possible connections among necroptosis, immune responses and MN death in the development of ALS and suggest the future 展开更多
关键词 NECROPTOSIS Th17 NERVE injury amyotrophic LATERAL SCLEROSIS
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