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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

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Neural Regeneration Research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen Zhu Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto *** mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy *** aggregates alter protein-protein interactions and compromise transcriptional *** this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

关键词： androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model neurodegeneration neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-βstory

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Neural Regeneration Research 2023年第1期18卷 117-118页

作者： Bruno P.Imbimbo Claudia Balducci Stefania Ippati Mark Watling department of Research&Development Chiesi FarmaceuticiParmaItaly department of Neuroscience Istituto di Ricerche Farmacologiche“Mario Negri”IRCCSMilanItaly San Raffaele Scientific Institute San Raffaele HospitalMilanItaly cns&pain department TranScrip Ltd.ReadingUK

Tau is an important protein of the central nervous system formed by 352-441 amino acids and encoded by the MAPT(microtubule-associated protein tau)gene on chromosome 17 which generates 6 *** is located in axons,dendrites,nucleus,cell membrane,and synapses of *** protein is also expressed to a lesser extent in astrocytes and oligodendrocytes,although its role in these cells has been little *** protein is also present in the interstitial fluid and can cross into the cerebrospinal fluid(CSF)and reach the systemic circulation.

关键词： tau Alzheimer cerebrospinal

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So Li Zhang Haining Ou department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of cns Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Correlation between anxiety, depression, and social stress in young patients with thoracolumbar spine fractures

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World Journal of Psychiatry 2025年第1期15卷 83-92页

作者： Bo Wang Da Shi Yin-Di Sun Bo Dong Joint Ward of Orthopedics department of TCM Honghui HospitalXi'an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina pain Ward of Orthopedics department of TCM Honghui HospitalXi'an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina

BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar *** kind of fracture is easily combined with serious injuries to peripheral nerves and soft tissues,which causes paralysis of the lower limbs if there is no timely rehabilitation *** patients with thoracolumbar fractures find it difficult to recover after the operation,and they are prone to depression,low self-esteem,and other negative *** To investigate the association between anxiety,depression,and social stress in young patients with thoracolumbar spine fractures and the effect on rehabilitation *** This study retrospectively analyzed 100 patients admitted to the orthopedic department of Honghui Hospital,Xi’an Jiaotong University who underwent thoracolumbar spine fracture surgery from January 2022 to June *** general data of the patients were assessed with the Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),life events scale,and social support rating scale(SSRS)to identify the correlation between anxiety,depression scores,and social stress and social *** Japanese Orthopedic Association(JOA)was utilized to evaluate the rehabilitation outcomes of the patients and to analyze the effects of anxiety and depression scores on *** According to the scores of HAMD and HAMA in all patients,the prevalence of depression in patients was 39%(39/100),and the prevalence of anxiety was 49%(49/100).Patients were categorized into non-depression(n=61)and depression(n=39),non-anxiety(n=51),and anxiety(n=49)*** significant differences in gender,occupation,Pittsburgh Sleep Quality Index(PSQI)score,and monthly family income were observed between the non-depression and depression groups(P<0.05).A significant difference in occupation and PSQI score was found between the non-anxiety and anxiety *** depression(r=0

关键词： Patients with thoracolumbar fractures Anxiety Depression Social pressure Social support

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Spinal cord injury regenerative therapy development:integration of design of experiments

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Neural Regeneration Research 2025年第9期20卷 2571-2573页

作者： Yuji Okano Hideyuki Okano Yoshitaka Kase Division of cns Regeneration and Drug Discovery International Center for Brain Science(ICBS)Fujita Health UniversityKutsukake-ChoToyoake-ShiAichiJapan department of Extended Intelligence for Medicine The Ishii-Ishibashi LaboratoryKeio University School of MedicineShinanomachiShinjuku-KuTokyoJapan Keio University Regenerative Medicine Research Center Kawasaki-kuKawasaki-shiJapan

Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of *** continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPScns/PCs)into spinal cord injured tissues.

关键词： Spinal paralysis injury

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ON THE EXISTENCE OF LOCAL CLASSICAL SOLUTION FOR A CLASS OF ONE-DIMENSIONAL COMPRESSIBLE NON-NEWTONIAN FLUIDS

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Acta Mathematica Scientia 2015年第1期35卷 157-181页

作者：方莉李自来 cns and department of Mathematics Northwest University

In this paper, the aim is to establish the local existence of classical solutions for a class of compressible non-Newtonian fluids with vacuum in one-dimensional bounded intervals, under the assumption that the data satisfies a natural compatibility condition. For the results, the initial density does not need to be bounded below away from zero.

关键词： compressible non-Newtonian fluids vacuum local classical solution

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Are ATXN2 variants modifying our understanding about neural pathogenesis,phenotypes,and diagnostic?

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Neural Regeneration Research 2022年第11期17卷 2445-2447页

作者： Jose Miguel Laffita-Mesa Martin Paucar Per Svenningsson department of Clinical Neuroscience(cns) Karolinska Universitetssjukhuset

ATXN2 one gene with multiple phenotype effects:ATXN2 gene encodes a cytosolic protein(ataxin-2)with pleiotropic functions(see below).This gene contains a number of exonic Cytosine-Adenine-Guanine(CAG)-repeats which encodes a polyglutamine tract(polyQ)in the N-terminal intrinsically disordered region(IDR)of the ***2CAG repeats are interrupted by CAA codons which is relevant only for DNA and RNA but not for protein since CAA also encodes glutamine(Q).

关键词： pathogenesis neural interrupted

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Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

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Neural Regeneration Research 2025年第10期20卷 2923-2937页

作者： Yan Li Peng Hao Hongmei Duan Fei Hao Wen Zhao Yudan Gao Zhaoyang Yang Kwok-Fai So Xiaoguang Li department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina China Rehabilitation Science Institute China Rehabilitation Research CenterBeijing Key Laboratory of Neural Injury and RehabilitationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Guangdong-HongKong-Macao Institute of cns Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-HongKong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after ***,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains *** this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic *** findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated ***,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain *** findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

关键词： adult endogenous neurogenesis basic fibroblast growth factor-hyaluronic acid collagen gel cortical remodeling functional recovery migration motor cortex injury neural circuits neural stem cells newborn neurons proliferation

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