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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang Xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng College of Traditional Chinese Medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental Disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical Genetics and Center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Metabolic Diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese Medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

Primary parenchymal squamous cell carcinoma of the kidney:A case report

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World Journal of Clinical Cases 2025年第4期13卷 34-40页

作者： Zhi-Hui Zheng Bo Shao Chao-Min Xu Ke Wang Jia-Zhu Wen Li-Kang Luo Jia-Cheng Guan Department of Ultrasound The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Radiology Shulan(Quzhou)HospitalQuzhou 324000Zhejiang ProvinceChina Department of Radiology The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Pathology The Second people’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases *** SUMMARY This study reports a 51-year-old man with primary SCC of the renal *** patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross *** antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated *** patient underwent laparoscopic unilateral nephrectomy and lymph node *** pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and *** pathological stage was *** months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena *** patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease *** We report a case of primary SCC of the renal parenchyma,a rare renal *** clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis *** to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

关键词： Renal tumor Renal parenchyma Squamous cell carcinoma Renal calculi Computed tomography Case report