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

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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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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simple Kac-Moody groups with trivial schur multipliers

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science China Mathematics 2018年第2期61卷 311-316页

作者： Jun morita Institute of Mathematics University of Tsukuba

We obtain new examples of simple Kac-Moody groups with trivial schur multipliers.

关键词： Kac-Moody group simple group schur multiplier

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Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

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Experimental and Numerical Evaluation of the Performance of supersonic Two-stage High-Velocity Oxy-Fuel Thermal spray (Warm spray) Gun

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Journal of Thermal science 2011年第1期20卷 88-92页

作者： H.Katanoda H.morita M.Komatsu s.Kuroda Department of Mechanical Engineering Kagoshima University1-21-40 KorimotoKagoshima 890-0065Japan Hybrid Materials Center National Institute for Materials Science1-2-1SengenTsukubaIbaraki 305-0047Japan

The water-cooled supersonic two-stage high-velocity oxy-fuel (HVOF) thermal spray gun was developed to make a coating of temperature-sensitive material,such as titanium,on a *** gun has a combustion chamber (CC) followed by a mixing chamber (MC),in which the combustion gas is mixed with the nitrogen gas at room *** mixed gas is accelerated to supersonic speed through a converging-diverging (C-D) nozzle followed by a straight passage called the *** paper proposes an experimental procedure to estimate the cooling rate of CC,MC and barrel ***,the mathematical model is presented to predict the pressure and temperature in the MC for the specific mass flow rates of fuel,oxygen and nitrogen by assuming chemical equilibrium with water-cooling in the CC and MC,and frozen flow with constant specific heat from stagnant condition to the throat in the CC and ***,the present mathematical model was validated by comparing the calculated and measured stagnant pressures of the CC of the two-stage HVOF gun.

关键词： supersonic flow Two-stage HVOF thermal spray gun Warm spray

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Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber

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Microglial dysfunction and genetic risk for neurodegenerative disease

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Neural Regeneration Research 2025年第5期20卷 1401-1402页

作者： Debra s.MacDonald Jay Penney Department of Biomedical sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations *** tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com *** troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

关键词： degenerative diseases

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Experimental study on boundary lubricity of superficial area of articular cartilage and synovial fluid

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Friction 2024年第5期12卷 981-996页

作者： Wenxiao LI Takehiro morita Yoshinori sAWAE Departure of Mechanical Engineering Kyushu UniversityFukuoka8190395Japan International Institute for Carton-Neutral Energy Research Kyushu UniversityFukuoka8190395Japan Advanced Research Center for Biomechanics Kyushu UniversityFukuoka8190395Japan

The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in *** this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(sF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage ***,the frictional characteristics were examined in phosphate-buffered saline(PBs)and sF against *** reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage ***,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion *** coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in ***,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited *** the low COF group of specimens,all four treatments increased the COF in PBs to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by *** means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage *** variation in the COF of the cartilage specimens was suppressed in sF because it had a clear boundary lubrication effect on the cartilage *** lubricating effect of sF could be confirmed even after degenerative treatment.

关键词： articular cartilage synovial fluid the uppermost superficial layer boundary lubrication

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semantic segmentation of Lumbar Vertebrae Using Meijering U-Net(MU-Net)on spine Magnetic Resonance Images

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Computer Modeling in Engineering & sciences 2025年第1期142卷 733-757页

作者： Lakshmi s V V shiloah Elizabeth Darmanayagam sunil Retmin Raj Cyril Department of Computer science and Engineering College of Engineering GuindyAnna UniversityChennai600025India Department of Information Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower back pain is one of the most common medical problems in the world and it is experienced by a huge percentage of people *** to its ability to produce a detailed view of the soft tissues,including the spinal cord,nerves,intervertebral discs,and vertebrae,Magnetic Resonance Imaging is thought to be the most effective method for imaging the *** semantic segmentation of vertebrae plays a major role in the diagnostic process of lumbar *** is difficult to semantically partition the vertebrae in Magnetic Resonance Images from the surrounding variety of tissues,including muscles,ligaments,and intervertebral discs.U-Net is a powerful deep-learning architecture to handle the challenges of medical image analysis tasks and achieves high segmentation *** work proposes a modified U-Net architecture namely MU-Net,consisting of the Meijering convolutional layer that incorporates the Meijering filter to perform the semantic segmentation of lumbar vertebrae L1 to L5 and sacral vertebra ***-colour mask images were generated and used as ground truth for training the *** work has been carried out on 1312 images expanded from T1-weighted mid-sagittal MRI images of 515 patients in the Lumbar spine MRI Dataset publicly available from Mendeley *** proposed MU-Net model for the semantic segmentation of the lumbar vertebrae gives better performance with 98.79%of pixel accuracy(PA),98.66%of dice similarity coefficient(DsC),97.36%of Jaccard coefficient,and 92.55%mean Intersection over Union(mean IoU)metrics using the mentioned dataset.

关键词： Computer aided diagnosis(CAD) magnetic resonance imaging(MRI) semantic segmentation lumbar vertebrae deep learning U-Net model

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