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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

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Neural Regeneration Research 2025年第10期20卷 2862-2871页

作者： Prajakta Deshpande Anuradha Venkatakrishnan Chimata Amit Singh Department of Biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA Integrative Science and Engineering center University of DaytonDaytonOHUSA center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and *** acetylation is a common post-translational modification pivotal to basic cellular *** to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and *** this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in ***,we have focused on N-acetyltransferase 9 and its role in microtubule *** have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative *** have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

关键词： acetyl-coenzyme A Alzheimer’s disease animal models cell death drosophila eye human disease c-Jun N-terminal kinase signaling N-Acetyltransferases N-acetyltransferase 9 neurodegeneration

A new horizon for neuroscience:terahertz biotechnology in brain research

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Neural Regeneration Research 2025年第2期20卷 309-325页

作者： Zhengping Pu Yu Wu Zhongjie Zhu Hongwei Zhao Donghong Cui Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry Kangci Hospital of JiaxingTongxiangZhejiang ProvinceChina Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied PhysicsChinese Academy of ScienceShanghaiChina National Facility for Protein Science in Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain *** this article,we review the development of terahertz biotechnology and its applications in the field of *** evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin *** vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric *** the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic ***,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical *** review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

关键词： biological effect brain neuron neuropsychiatry neuroscience non-thermal effect terahertz imaging terahertz radiation terahertz spectroscopy terahertz technology

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

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

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

Unraveling post-growth mechanisms of monolayer CsPbBr3 nanocubes:Laser-enhanced transformations and cathodoluminescence-electron microscopy correlations

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Journal of Energy Chemistry 2025年第1期100卷 146-156页

作者： Mingxing Li Xiaoge Wang Xiaofan Cao Zhiqun He Chunjun Liang Mingxing Chen Jing Ju Fangtian You Key Laboratory of Luminescence and Optical Information Ministry of Education Institute of Optoelectronic Technology Beijing Jiaotong University Beijing National Laboratory for Molecular sciences (BNLMS) College of Chemistry and Molecular Engineering Peking University

Lead-halide perovskite nanoparticles（LHP NPs） are highly promising materials for next-generation displays and solid-state lighting due to their exceptional optical properties. However, their inherent instability presents a significant challenge. Recent advances have demonstrated that optoelectronic devices based on monolayer nanoparticle films exhibit both high luminescence efficiency and long-term *** research demonstrates that mobility limitations and anisotropic alignments in CsPbBr3nanocube monolayer films are key to their stabilization, hindering spontaneous growth through face-to-face fusion and resulting in the formation of connecting necks in a diagonal direction. Introducing laser irradiation confirmed this by significantly accelerating nanocubes growth, increasing mobility, and enhancing local structural ordering, leading to larger and more regularly shaped nanosheets. Fourier transform infrared spectroscopy and energy dispersive spectroscopy line-scan analyses indicated that laser irradiation did not disrupt the ligand structure. Transmission electron microscopy and correlative cathodoluminescence electron microscopy revealed the effects of post-growth and heterogeneous structures, including enhanced luminescence and inhomogeneous intensity in the nanosheets. These findings deepen the understanding of the post-growth mechanism of monolayer nanoparticles and the structure-emission correlation and highlight the unique role of laser irradiation in directing the formation of well-defined and regular nanostructures.

关键词： Post-growth mechanism Heterogeneous structure Single-particle spectroscopy Laser irradiation

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin university of Traditional Chinese Medicine TianjinChina Characteristic Medical center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

Combinatorial therapies for spinal cord injury repair

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Neural Regeneration Research 2025年第5期20卷 1293-1308页

作者： Carla S.Sousa Andreia Monteiro António J.Salgado Nuno A.Silva Life and health sciences Research Institute(ICVS) School of MedicineUniversity of MinhoCampus de Gualtar-gualtarBragaPortugal ICVS/3B’s Associate Lab PT Government Associated LabCampus de Gualtar-gualtarBragaPortugal

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

关键词： electric stimulation neural tissue regeneration neuroprotection polytherapy spinal cord injury