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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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

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

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed wMatthijs Blankesteijn sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-school for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-school for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(csVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term csVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CsVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek w.wheeler Giorgio A.Ascoli Center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study Bioengineering Department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

Controversies in fecal incontinence

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world Journal of Gastroenterology 2025年第3期31卷 113-119页

作者： Andreia Albuquerque satish s C Rao school of Medicine and Biomedical sciences Fernando Pessoa UniversityGondomar 4420-096PortoPortugal Precancerous Lesions and Early Cancer Management Research Group RIsE@CI-IPO(Health Research Network) Portuguese Oncology Institute of PortoPorto 4200-072Portugal Division of Gastroenterology and Hepatology Department of Internal MedicineAugusta UniversityAugustaGA 30912United States

Fecal incontinence is a common condition that can significantly impact patients’quality of *** anal sphincter injury and anorectal surgeries are common *** ultrasound and anorectal manometry are important diagnostic tools for evaluating *** are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and *** this editorial,we will discuss current controversies and novel approaches to fecal *** for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected *** Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal *** tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and *** biofeedback therapy can overcome some limitations of the office-based *** muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment *** neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.

关键词： Fecal incontinence Endoanal ultrasound Anal sphincter defects Biofeedback Neuropathy sacral neuromodulation

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

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

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles w.Plant Department of Neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy