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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

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

Deep tissue near-infrared imaging for vascular network analysis

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Journal of Innovative Optical Health sciences 2017年第3期10卷 12-23页

作者： Kübra seker Mehmet Engin Department of Electrical&Electronics Engineering Faculty of Engineering Ege University Bornova IzmirTurkey35100

subcutaneous vein network plays important roles to maintain microcirculation that is related to some diagnostic *** developments of optical imaging technologies,still the difficulties about deep skin vascular imaging have been *** the other hand,since hemoglobin con-centration of human blood has key role in the veins imaging by optical manner,the used wavelength in vascular imaging,must be chosen considering absorption of *** this research,we constructed a near infrared(NIR)light source because of lower absorption of hemoglobin in this optical *** obtain vascular image,reflectance geometry was ***,from recorded images,vascular network analysis,such as calculation of width of vascular of interest and complexity of selected region were *** comparing with other modalities,we observed that proposed imaging system has great advantages including nonionized radiation,moderate penetration depth of 0.5-3 mm and diameter of 1 mm,cost-effective and algorit hmic simplicity for analysis.

关键词： Vascular NIR imaging manufacturing liquid and solid phantoms difuse optical imaging image processing and analysis optical imaging system design.

The movement dynamics of autotomized lizards and their tails reveal functional costs of caudal autotomy

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Integrative Zoology 2020年第6期15卷 511-521页

作者： Irene FERNÁNDEZ-RODRÍGUEZ Florentino braÑA Department of Organisms and systems Biology(Zoology) University of OviedoOviedoSpain Research Unit of Biodiversity(UMIB UO/CSIC/PA)University of OviedoMieresSpain

Autotomy has evolved independently several times in different animal *** frequently involves immediate functional costs,so regeneration evolved in many instances to restore the functionality of that body *** autotomy is a widespread antipredator strategy in lizards,although it may affect energy storage,locomotion dynamics,or survival in future encounters with ***,we assessed the effect of tail loss on the locomotor performance of wall lizards(Podarcis muralis),as well as the recovery of locomotor functionality of lizards with regenerated tails,and the movement dynamics of shed tails that were either intact or having regenerated *** loss had no effect on locomotion over unhindered spaces,possibly due to compensation between a negative effect on the stride of front limbs,and a positive effect of losing mass and friction *** found a clear negative impact of tail loss on locomotion in spaces with interspersed obstacles,in which tailed lizards jumped larger distances when leaving the ***,lizards that used the tail to push off the ground were able to approach the obstacles from further,so that the tail seemed to be useful when used during *** fully restores lizard’s locomotor capacities,but tail antipredator value,as indicated by the intensity of post-autotomic movements,is only partially *** these results,we propose that,together with the recovery of post-autotomy antipredator capacities,the restoration of the organismal locomotor performance may have been an important,yet frequently neglected factor in the evolution of lizard’s regeneration ability.

关键词： autotomy locomotor performance regeneration tail wall lizard

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

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

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

Comparison of clinical outcomes of deep anterior lamellar keratoplasty and excimer laser assisted anterior lamellar keratoplasty in keratoconus

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 582-586页

作者： Kübra serbest Ceylanoglu Bahri Aydin Mehmet Cuneyt Ozmen Department of Ophthalmology Sincan State Hospital Department of Ophthalmology Gazi University Medical School

AIM: To compare and evaluate the clinical outcomes of deep anterior lamellar keratoplasty(DALK) and excimer laser assisted anterior lamellar keratoplasty(ELLK) in eyes with ***: In this study, 57 eyes of 56 patients operated between 2013 to 2017 were included. Thirty-one eyes underwent big-bubble DALK and twenty-six eyes underwent ELLK. Preoperative and at control visits complete ophthalmic examination was performed. REsULTs: The mean patient age at the time of DALK surgery was 27 y and mean follow-up period was 21±5.4 mo. The mean patient age at the time of ELLK surgery was 27 y and mean follow-up period was 40±18 mo. Mean best spectacle corrected visual acuity(BsCVA) at postoperative period was significantly higher for DALK group(0.66±0.11) versus ELLK group(0.4±0.2)(Pscemet's membrane microperforation was occurred in 7 patients in DALK group versus in 1 patient in ELLK group. In 4 eyes, interface irregularity was developed in ELLK group. None of the patients in follow-up had graft rejection in both ***: In ELLK group, complication rate is lower, the surgical technique is simpler, faster and safer and also ELLK requires less experience with respect to DALK. Further, DALK can be performed unless satisfactory visual acuity is achieved after ELLK.

关键词： excimer laser assisted lamellar keratoplasty deep anterior lamellar keratoplasty big-bubble technique