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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

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru Hidenori Suzuki department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

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A-kinase anchoring protein-mediated compartmentalization of pro-survival signaling in the retina

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Neural Regeneration Research 2025年第2期20卷 479-480页

作者： Joanna Mackiewicz Tomasz Boczek department of Molecular Neurochemistry Medical University of LodzLodzPoland

The retina plays a fundamental role in the process of vision,serving as the primary interface between external visual stimuli and the central nervous *** the retina is exposed to a variety of environmental stresses and deleterious insults,it is susceptible to a spectrum of pathological conditions that can detrimentally affect *** often leads to irreversible vision loss due to the injury of specific cell *** instance,inherited retinal degeneration and age-related macular degeneration can lead to the death of photoreceptors,while conditions like glaucoma and optic nerve injury can result in the loss of ganglion *** precise pathological mechanisms driving retinal degeneration remain largely elusive,although research utilizing mouse models suggests that disruptions in intracellular signal transduction pathways may play a pivotal *** pathways within the retina orchestrate various aspects of retinal physiology,including phototransduction,synaptic transmission,and neuronal survival.

关键词： degeneration utilizing irreversible

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Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli department of Molecular and Translational Medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

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Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3229-3230页

作者： Savina Apolloni Nadia D’Ambrosi department of Biology University of Rome Tor VergataRomeItaly

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and *** the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 *** is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.

关键词： STAT3 dissection sclerosis

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Nano-Enhanced Dairy Scum Biodiesel Blends:Unleashing the Power of Aluminium Oxide for Sustainable and Efficient Engine Performance

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Journal of Thermal Science 2025年第1期 283-302页

作者： Veeranna MODI Prasad B.RAMPURE Sunil Kumar SHETTY Madeva NAGARAL Channa Keshava NAIK N Johar MGM Muhammad Irsyad ABDULLAH Abdullah I.AL-MANSOUR Shamshad ALAM KLE College of Engineering and Technology ChikodiVisvesvaraya Technological University Nitte (Deemed to be university) NMAM Institute of Technology (NMAMIT)Department of Mechanical Engineering Aircraft Research and Design Centre HAL department of Mechanical Engineering BGS College of Engineering and TechnologyBengaluruAffiliated to Visvesvaraya Technological University Management and Science university department of Civil Engineering College of EngineeringKing Saud University

This study investigates the effect of aluminium oxide nanoparticlesaddition to biodiesel blends made from dairy milk scum on performance and combustion characteristics of the diesel *** dispersion of Al2O3nanoparticles in B20 blends at different concentrations was done with the help of *** number of blends were prepared for the *** Machine learning algorithms(Random Forest（RF）and CatBoost) was used for the *** results show that in comparison to biodiesel blends without nanoparticles,the kinematic viscosity and density is higher for fuel blends with *** these Fuel blends have higher calorific *** blends exhibited reduced Brake Specific Fuel Consumption（BSFC） of2.85% than the blends without nano particles(Dairy Scum Methyl Ester Biodiesel 20%+Neat Diesel 80%（in volume）,DSMEB20),57.14% less CO,40.8% less hydrocarbon,and increased NOxemissions compared to conventional diesel,contributing to the development of environmentally friendly and renewable biofuel blends with *** B20NP30 is the optimal blend for performance and emission *** study concludes with findings on enhanced Brake Thermal Efficiency（BTE） of 26.29% in 3×10-5（in volume） Al2O3nanoparticle-blended DSME B20 and other DSME B20 fuel blends,emphasizing the importance of optimal nanoparticle *** correlation matrix shows how engine load,efficiency measures（BTE,BSFC）,and emissions（CO,CO2,NOx,Smoke） are connected in complex *** results help us understand the complicated dynamics of engine performance and emission characteristics ***'s diagram for BTE and BSFC shows that CatBoost-based BTE models perform superior to RF-based models during the training as well as testing *** results were obtained for CO and CO2emission results.

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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub Program in Neuroscience Indiana UniversityBloomingtonINUSA department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud university Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud university Medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

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Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.P.Sakamuri Anil Sakamuri department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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