المؤلفون: Huajing You, Tengteng Wu, Gang Du, Yue Huang, Yixuan Zeng, Lishan Lin, Dingbang Chen, Chao Wu, Xunhua Li, Jean-marc Burgunder, Zhong Pei

المصدر: Frontiers in Neurology, Vol 12 (2021)

مصطلحات موضوعية: Huntington's disease, glial fibrillary acidic protein, neurofilament light protein, clinical severity, biomarker, Neurology. Diseases of the nervous system, RC346-429

الوصف: Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD.Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity.Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2.Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2021.779890/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/7597e9b8b9594d0e9cd79cb62e077540Test

المؤلفون: Chao Wu, Qiong Cai, Huajing You, Xiangxue Zhou, Dingbang Chen, Guiling Mo, Xunhua Li

المصدر: Molecular Genetics & Genomic Medicine, Vol 7, Iss 6, Pp n/a-n/a (2019)

مصطلحات موضوعية: ATXN2, ATXN3, modifier, oculomotor, spinocerebellar ataxia, Genetics, QH426-470

الوصف: Abstract Background The presence of more than one polyQ‐related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes. Methods We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and oculomotor performances were investigated. The age at onset and oculomotor parameters of both patients were compared with matched pure SCA3 groups controlling either disease severity or CAG repeats. Results Most of the clinical phenotypes and oculomotor characteristics of these two patients were common to typical SCA3 patients. Compared to pure SCA3 groups controlling disease severity, mild reduced horizontal saccade velocity could be detected in both patients. However, mild expansions of the ATXN2 allele seemed to have no influence on the age at onset of Patient 1 but might have a mild impact on Patient 2. Conclusion Our study provides supporting evidence that mild expansions of ATXN2 may have modifying effects on SCA3 phenotype. Larger control series and longitudinal data are warranted to confirm our results.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2324-9269Test

الوصول الحر: https://doaj.org/article/d149d41c72c141048938b0485d5091aaTest

المؤلفون: Jie Yang, Dingbang Chen, Li Feng, Zhicong Yan, Chao Wu, Huajing You, Bing Liao, Jinlang Wu, Xunhua Li

المصدر: Neurological Sciences. 43:2137-2139

مصطلحات موضوعية: Psychiatry and Mental health, Neurology (clinical), Dermatology, General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::77fa3d0eef71738ba84c957c6148d793Test
https://doi.org/10.1007/s10072-021-05788-wTest

المؤلفون: Jie Yang, Zihuan Huang, Huiming Yang, Yue Luo, Huajing You, Dingbang Chen, Zhong Pei, Xunhua Li

المصدر: Parkinsonismrelated disorders. 95

مصطلحات موضوعية: Neurology, Hepatolenticular Degeneration, Intermediate Filaments, Humans, Neurology (clinical), Geriatrics and Gerontology, Atrophy, Magnetic Resonance Imaging, Biomarkers

الوصف: Neurofilament light chain (NfL) was recently proposed as a promising blood biomarker for nervous system diseases, including Wilson's disease (WD). In this study, we investigated plasma NfL concentrations in patients with different types of WD and their correlations with clinical manifestations and brain atrophy.Seventy-five WD cases (54 neurological type, 21 hepatic type) and 27 age-matched healthy controls were included in this study. We compared plasma NfL concentrations between the different types and correlated them with Unified Wilson's Disease Rating Scale (UWDRS) scores. Patients were allocated to stable and unstable groups according to changes in UWDRS scores and clinical assessment. We compared the differences in plasma NfL concentrations between groups. Voxel-based morphometry (VBM) and FreeSurfer software were used to analyze MRI images. We investigated the correlation between plasma NfL concentrations and volume of gray matter, white matter, and several areas of interest in the brain MRI of 24 patients.Plasma NfL concentrations were significantly higher in neurological type WD than in hepatic type WD (8.16 vs. 3.19 pg/mL, p 0.001). Plasma NfL concentrations were positively correlated with UWDRS scores (r = 0.291, p = 0.035) in patients with neurological type WD. Plasma NfL was significantly higher in unstable patients than in stable patients (10.74 vs. 7.23 pg/mL, p = 0.004). Significant negative associations were found between plasma NfL level and the volumes of total gray matter, bilateral caudate nucleus, putamen, and nucleus accumbens.Plasma NfL is valuable as a biomarker for neurological damage in patients with WD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::856380c41a020850dfdd375c7466041fTest
https://pubmed.ncbi.nlm.nih.gov/34942565Test

المؤلفون: Huajing You (11727614), Tengteng Wu (11727617), Gang Du (694334), Yue Huang (285485), Yixuan Zeng (5818343), Lishan Lin (4721967), Dingbang Chen (11727620), Chao Wu (199897), Xunhua Li (11727623), Jean-marc Burgunder (11727626), Zhong Pei (316477)

مصطلحات موضوعية: Neurology and Neuromuscular Diseases, Neurogenetics, Huntington's disease, glial fibrillary acidic protein, neurofilament light protein, clinical severity, biomarker

الوصف: Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD. Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity. Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2. Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

العلاقة: https://figshare.com/articles/dataset/Table_1_Evaluation_of_Blood_Glial_Fibrillary_Acidic_Protein_as_a_Potential_Marker_in_Huntington_s_Disease_DOCX/17046620Test

الإتاحة: https://doi.org/10.3389/fneur.2021.779890.s001Test

المؤلفون: Chao Wu, Huajing You, Zhong Pei, Xue‐jiao Li, Hui-Hua Yang, Hong-Yu Zhang, Qing-Ling Fu, Yukun Feng, Tengteng Wu, Xunhua Li, Shu-Bin Fang, Ge Li

المصدر: Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-11 (2020)
Stem Cell Research & Therapy

مصطلحات موضوعية: Machado-Joseph disease, Mesenchymal stem cell-derived exosomes, Medicine (miscellaneous), Neuropathology, Exosomes, Biochemistry, Genetics and Molecular Biology (miscellaneous), Motor function, lcsh:Biochemistry, Mice, Cerebellum, Animals, Effective treatment, Medicine, lcsh:QD415-436, Neuroinflammation, lcsh:R5-920, business.industry, Research, Mesenchymal stem cell, Mesenchymal Stem Cells, Cell Biology, medicine.disease, Microvesicles, Disease Models, Animal, Cancer research, Molecular Medicine, Stem cell, lcsh:Medicine (General), business, Machado–Joseph disease

الوصف: Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e11e899325b354b2cb971b6169e837d8Test
https://doi.org/10.1186/s13287-020-01727-2Test

المؤلفون: Dingbang Chen, Li Feng, Chao Wu, Jiwei Zhang, Xiang-xue Zhou, Xiu-Ling Liang, Huajing You, Zhong Pei, Xun-hua Li

المصدر: CNS neurosciencetherapeutics. 23(4)

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Ataxia, genetic structures, Severity of Illness Index, Smooth pursuit, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Ocular Motility Disorders, Physiology (medical), medicine, Humans, Pharmacology (medical), Ataxin-3, Pharmacology, Video-oculography, business.industry, Machado-Joseph Disease, Original Articles, Middle Aged, medicine.disease, Biomarker (cell), Repressor Proteins, Psychiatry and Mental health, 030104 developmental biology, Saccade, Cohort, Fixation (visual), Mutation, Spinocerebellar ataxia, Disease Progression, Female, medicine.symptom, business, Mental Status Schedule, Neuroscience, 030217 neurology & neurosurgery

الوصف: AIMS: To detect specific oculomotor deficits in preclinical stage of spinocerebellar ataxia type 3 (SCA3) and evaluate whether these abnormalities prove useful as potential biomarkers of disease progression. METHODS: A Chinese cohort of 56 patients with SCA3, including 12 preclinical carriers of SCA3 (pre‐SCA3) and 44 manifest SCA3, and 26 healthy control individuals were recruited. We performed a detailed investigation on central oculomotor performance including fixation, gaze, smooth pursuit, prosaccade, and antisaccade using video‐oculography. RESULTS: Common oculomotor features of pre‐SCA3 included square‐wave jerk during central fixation and gaze holding, impaired vertical smooth pursuit, slow upward saccade, and increased antisaccade error rate. In our SCA3 cohort, all oculomotor parameters were correlated with the score of the Scale for the Assessment and Rating of Ataxia, whilst some of them were correlated with disease duration. CONCLUSION: This study showed that a series of neuropathological changes reflected by oculomotor abnormalities appeared preferentially in preclinical stage of SCA3. Accordingly, objective oculomotor preclinical signs may be useful to detect the optimum time‐point for therapeutic interventions in future clinical trials of SCA3. Larger and longitudinal data are warranted to confirm our results.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6b0826404b385b488cc4ce1de65cbbeTest
https://pubmed.ncbi.nlm.nih.gov/28195427Test

المؤلفون: Qiong Cai, Chao Wu, Huajing You, Xiangxue Zhou, Gui-ling Mo, Dingbang Chen, Xunhua Li

المصدر: Molecular Genetics & Genomic Medicine, Vol 7, Iss 6, Pp n/a-n/a (2019)
Molecular Genetics & Genomic Medicine

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Proband, China, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Ataxia, lcsh:QH426-470, Nerve Tissue Proteins, 030105 genetics & heredity, Gastroenterology, 03 medical and health sciences, spinocerebellar ataxia, Asian People, Disease severity, Internal medicine, Saccades, Genetics, medicine, Humans, Allele, Ataxin-3, Molecular Biology, Alleles, Genetics (clinical), Ataxin-2, Retrospective Studies, Slow saccades, modifier, business.industry, Incidence (epidemiology), Nuclear Proteins, ATXN3, ATXN2, oculomotor, Original Articles, medicine.disease, Phenotype, Repressor Proteins, lcsh:Genetics, 030104 developmental biology, Spinocerebellar ataxia, Female, Original Article, medicine.symptom, business

الوصف: Background The presence of more than one polyQ‐related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes. Methods We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and oculomotor performances were investigated. The age at onset and oculomotor parameters of both patients were compared with matched pure SCA3 groups controlling either disease severity or CAG repeats. Results Most of the clinical phenotypes and oculomotor characteristics of these two patients were common to typical SCA3 patients. Compared to pure SCA3 groups controlling disease severity, mild reduced horizontal saccade velocity could be detected in both patients. However, mild expansions of the ATXN2 allele seemed to have no influence on the age at onset of Patient 1 but might have a mild impact on Patient 2. Conclusion Our study provides supporting evidence that mild expansions of ATXN2 may have modifying effects on SCA3 phenotype. Larger control series and longitudinal data are warranted to confirm our results.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eef49bc3b027556676bcb68b9f04a31fTest
https://doi.org/10.1002/mgg3.663Test