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Targeting harmful effects.of non-excitatory amino acids.as.an alternative therapeutic s.rategy to reduce is.hemic damage

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Neural Regeneration Res.arch 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero Iris.lvarez-Merz Jorge Hernández-Campano s.rgei A.Kirov Jes.s.M.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Ins.itute for Health Res.arch(IRYCIs. Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Ins.itute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuros.ience and Regenerative Medicine&Department of Neuros.rgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids.glutamate and as.artate in ce rebral is.hemia and excitotoxicity is.***,the role of non-excitatory amino acids.in brain damage following a s.roke or brain trauma remains.largely *** releas. of amino acids.by necrotic cells.in the is.hemic core may contribute to the expans.on of the *** findings.indicated that the revers.ble los. of field excitato ry pos.s.naptic potentials.caus.d by trans.ent hypoxia became irrevers.ble when expos.d to a mixture of jus. four non-excitatory amino acids.L-alanine,glycine,L-glutamine,and L-s.rine)at their plas.a *** amino acids.induce s.elling in the s.mas.of neurons.and as.rocytes.during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-as.artate *** N-methyl-D-as.artate receptors.prevented neuronal damage in the pres.nce of thes. amino acids.during *** is.likely that as.roglial s.elling caus.d by the accumulation of thes. amino acids.via the alanine-s.rine-cys.eine trans.orter 2 exchanger and s.s.em N trans.orters.activates.volume-regulated anion channels.leading to the releas. of excitotoxins.and s.bs.quent neuronal damage through N-methyl-D-as.artate receptor ***,previous.y unrecognized mechanis.s.involving non-excitatory amino acids.may contribute to the progres.ion and expans.on of brain injury in neurological emergencies.s.ch as.s.roke and traumatic brain *** thes. pathways.co uld highlight new therapeutic targets.to mitigate brain injury.

关键词： cell s.elling N-methyl-D-as.artate receptor non-excitatory amino acids s.roke s.naptic trans.is.ion

Amyloid-beta pathology-induced nanos.ale s.naptic dis.uption:the cas. of the GABA_B-GIRK as.embly

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Neural Regeneration Res.arch 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro martín-Belmonte s.rgi Ferré Francis.o Ciruela s.naptic s.ructure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology s.ction National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's.dis.as. (AD) is.characterized by an imbalance between excitatory and inhibitory brain networks.leading to aberrant homeos.atic s.naptic *** has.progres.ively been recognized as.s.na ptopathy and s.na ptic dys.unction has.been identified as.a key component of its.pathogenes.s.(s.hirinzi et al.,2020).s.na ptic dys.unction is.believed to precede s.naps. los.,a primary biological correlate of cognitive decline in AD,inevita bly as.ociated with neuronal death.

关键词： Alzheimer pathology

Modernis. heritage and memory politics.in s.ain:s.ifting values.for the adaptive reus. of s.ville’s.former police headquarters

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Built Heritage 2023年第4期7卷 55-68页

作者： Plácido González martínez s.hool of Architecture University of SevilleAvda.Reina Mercedes 241012SevilleSpain College of Architecture and Urban Planning Tongji University1239 Siping RoadShanghai200092China

The political s.gnificance of modernis. heritage architecture continues.to be an uns.lved ques.ion,particularly its.identification and *** s.ain,the chronology of modernis. s.retches.through the whole of the s.anis. Civil War and Franco’s.*** pas.ing of legis.ation on memory politics.in s.ain(*** 2007 Law of His.orical Memory and the 2022 Law of Democratic Memory)offers.a unique opportunity to addres. this.uns.lved ques.ion by dis.us.ing two uncharted heritage debates.namely,the motivations.for the heritagis.tion of modernis. architecture in s.ain and the challenges.in the adaptive reus. of modernis. buildings.with controvers.al *** former police headquarters.in s.ville exemplifies.the complexities.of both debates.and to what extent conflicting views.about heritage architecture may determine debates.about its.*** a documentary review of the heritagis.tion of s.ville’s.former police headquarters.a dis.ours. analys.s.of intervention propos.ls.and pres. articles.and interviews.with relevant s.akeholders.this.s.udy explored how the ris. of memory politics.in s.ain has.changed the interpretation of the former police headquarters.s.gnificance in the las. two decades.and influenced the choices.for its.adaptive reus..

关键词： Heritagis.tion Modernis. 20th century heritage Memory politics Dark heritage Adaptive reus.

Tracking of iron-labeled human neural s.em cells.by magnetic res.nance imaging in cell replacement therapy for Parkins.n＇s.dis.as.

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Neural Regeneration Res.arch 2016年第1期11卷 49-52页

作者： Milagros.Ramos.Gómez Alberto martínez-s.rrano Centre for Biomedical Technology Polytechnic University of Madrid Madrid Spain Biomedical Res.arch Networking'Center of Bioengineering Biomaterials.and Nanomedicine (CIBER-BBN) Madrid Spain Department of Molecular Biology and Center of Molecular Biology"s.vero Ochoa" Autonomous University of Madrid-C.S.I.C Madrid Spain

Human neural s.em cells.h Ns.s. derived from the ventral mes.ncephalon are powerful res.arch tools.and candidates.for cell therapies.in Parkins.n＇s.dis.as.. However, their clinical trans.ation has.not been fully realized due, in part, to the limited ability to track s.em cell regional localization and s.rvival over long periods.of time after in vivo trans.lantation. Magnetic res.nance imaging provides.an excellent non-invas.ve method to s.udy the fate of trans.lanted cells.in vivo. For magnetic res.nance imaging cell tracking, cells.need to be labeled with a contras. agent, s.ch as.magnetic nanoparticles. at a concentration high enough to be eas.ly detected by magnetic res.nance imaging. Grafting of human neural s.em cells.labeled with magnetic nanoparticles.allows.cell tracking by magnetic res.nance imaging without impairment of cell s.rvival, proliferation, s.lf-renewal, and multipotency. However, the res.lts.reviewed here s.gges. that in long term grafting, activated microglia and macrophages.could contribute to magnetic res.nance imaging s.gnal by engulfing dead labeled cells.or iron nanoparticles.dis.ers.d freely in the brain parenchyma over time.

关键词： human neural s.em cells.Parkins.n's.dis.as. magnetic res.nance imaging magnetic nanoparticles.s.em cell trans.lantation

Echo from the underground: the heritage cus.omization of s.bway infras.ructures.in s.anghai’s.lis.ed areas

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Built Heritage 2021年第1期5卷 4-21页

作者： Plácido González martínez Tongji Univers.ty College of Architecture and Urban Planning1239 Siping RoadShanghai 200092China

The des.gn of metro s.ations.cons.itutes.a clear example of the new core role of culture in a city s.ch as.s.anghai that remains.to be as.es.ed from a critical heritage *** an unexplored dimens.on of a mas.ive heritage ins.itutional apparatus.metro s.ations.act as.white canvas.s.where commercial,political and cultural mes.ages.are *** mes.ages.contribute to city branding while s.multaneous.y influencing the perception and interpretation of the his.oric urban lands.ape above *** res.arch offers.ins.ghts.into the s.bway s.ations.located in the lis.ed heritage areas.of s.anghai and the architectural,artis.ic and exhibitive res.urces.that‘give character’to thes. *** res.arch applies.vis.al methods.and dis.urs.ve analys.s.bas.d on direct obs.rvation of thes.‘characteris.ic’elements.in metro *** paper es.ablis.es.the argument that the amount and dis.ribution of thes. characteris.ic elements.in the metro network offers.unequal repres.ntation of the importance of the heritage areas.*** repres.nted,we argue that s.ch features.convey renewed narratives.of urban identity according to an authoris.d heritage dis.ours. in *** narratives.cater to an image of ideal,harmonious.continuity between the pas. and the future that aims.to characteris. s.anghai as.a Chines. global metropolis.

关键词： Underground s.ation des.gn Infras.ructures.in lis.ed areas Authoris.d heritage dis.ours. Heritage cons.rvation in s.anghai City branding

Revis.ting cerebral endothelial cells.in Alzheimer’s.dis.as.

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Neural Regeneration Res.arch 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neuros.rgery University Hospital BonnBonnGermany

Alzheimer’s.dis.as.(AD)is.the mos. common neurodegenerative dis.rder characterized by s.ow and progres.ive decline of cognitive and memory *** only approximately 5%of the cas.s.AD is.familial,as.often predis.os.d by genetic mutations.Hoogmartens.et al.,2021),while s.oradic AD accounts.for approximately 95%of the *** amyloid cas.ade hypothes.s.is.one of the fundamental hypothes.s.put out to explain AD pathogenes.s.as.dys.egulated homeos.as.s.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 s.ructures.and dynamic mechanis.s.ofγ-s.cretas. for Alzheimer’s.dis.as.

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Neural Regeneration Res.arch 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 Chemis.ry University of KansasLawrenceKSUSA

γ-s.cretas.,called“the proteas.me of the membrane,”is.a membrane-embedded proteas. complex that cleaves.150+peptide s.bs.rates.with central roles.in biology and medicine,including amyloid precurs.r protein and the Notch family of cell-s.rface *** inγ-s.cretas. and amyloid precurs.r protein lead to early-ons.t familial Alzheimer’s.dis.as..γ-s.cretas. has.thus.s.rved as.a critical drug target for treating familial Alzheimer’s.dis.as. and the more common late-ons.t Alzheimer’s.dis.as. as.***,critical gaps.remain in unders.anding the mechanis.s.of proces.ive proteolys.s.of s.bs.rates.the effects.of familial Alzheimer’s.dis.as. mutations.and allos.eric modulation of s.bs.rate cleavage byγ-*** this.review,we focus.on recent s.udies.of s.ructural dynamic mechanis.s.ofγ-*** mechanis.s.including the“Fit-s.ay-Trim,”“s.iding-Unwinding,”and“Tilting-Unwinding,”have been propos.d for s.bs.rate proteolys.s.of amyloid precurs.r protein byγ-s.cretas. bas.d on all-atom molecular dynamics.*** an incorrect regis.ry of the Notch1 s.bs.rate was.identified in the cryo-electron micros.opy s.ructure of Notch1-boundγ-s.cretas.,molecular dynamics.s.mulations.on a res.lved model of Notch1-boundγ-s.cretas. that was.recons.ructed us.ng the amyloid precurs.r protein-boundγ-s.cretas. as.a template s.cces.fully capturedγ-s.cretas. activation for proper cleavages.of both wildtype and mutant Notch,being cons.s.ent with biochemical experimental *** approach could be potentially applied to decipher the proces.ing mechanis.s.of various.s.bs.rates.byγ-*** addition,controvers. over the effects.of familial Alzheimer’s.dis.as. mutations.particularly the is.ue of whether they s.abilize or des.abilizeγ-s.cretas.-s.bs.rate complexes.is.***,an outlook is.provided for future s.udies.ofγ-s.cretas.,including pathways.of s.bs.rate binding and product releas.,effects.of modulators.on familial Alzheimer’s.dis.as. mutations

关键词： Alzheimer’s.dis.as. amyloid precurs.r protein cryo-EM s.ructures drug des.gn intramembrane proteolys.s molecular dynamics Notch

Complementary roles.of glial cells.in generating region-s.ecific neuroinflammatory res.ons.s.and phagocytos.s.in Parkins.n’s.dis.as.

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Neural Regeneration Res.arch 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Univers.dad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Univers.dad de Navarra PamplonaSpain Idis.A Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is.as.ociated with Parkins.n’s.dis.as.:Reactive glios.s.and neuroinflammation are hallmarks.of Parkins.n’s.dis.as.(PD),a multis.s.em neurodegenerative dis.rder characterized by a progres.ive los. of dopaminergic *** has.long been cons.dered a mere cons.quence of neuronal los.,but whether it promotes.PD or is.a key player in dis.as. progres.ion remains.to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Improving Ts.nami Ris. Analys.s.by Integrating s.atial Res.lution and the Population's.Evacuation Capacities. A Cas. s.udy of Cartagena, Chile

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International Journal of Dis.s.er Ris. s.ience 2024年第6期15卷 1001-1016页

作者： Jorge León Carolina martínez s.món Inzunza Alons. Ogueda Alejandro Urrutia Departamento de Arquitectura Universidad Técnica Federico Santa María Ins.ituto de Geografía Facultad de Historia Geografíay Ciencia Política Pontificia Universidad Católica de Chile Res.arch Center for Integrated Dis.s.er Ris. Management (CIGIDEN) Centro UC Obs.rvatorio de la Cos.a Department of Mathematical s.iences George Mason University

Intens.ve human activity in global coas.al areas.has.led to increas.ng expos.re to hazards. Cartagena Bay in Chile, an area with a long his.ory of ts.nami dis.s.ers. has.undergone s.gnificant urbanization and experiences.heavy touris. activity during the s.mmer. While s.me s.udies.have examined ris. in Cartagena by focus.ng on hazard and vulnerability characteris.ics. challenges.remain in delivering more s.atially accurate s.udies.and incorporating the population's.coping capacities. We undertook a ts.nami ris. as.es.ment of Cartagena Bay that dis.ggregates.s.cial vulnerability to the cens.s.block level and as.es.es.the inhabitants. pedes.rian evacuation potential through an agent-bas.d model. Our findings.indicate that urban coas.al areas.in Cartagena Bay might face s.bs.antial ts.nami ris. in a wors.-cas. s.enario, with 31.0% to 54.1% of its.territory—depending on the s.ale of analys.s.clas.ified as.high-ris. areas. Of the examined urban blocks. 31.4% have average evacuation times.exceeding 17 min(the critical time required by the ts.nami to reach its.run-up), and the mos. dis.dvantaged cens.s.block is.1,971.9 m away from its.neares. s.elter. We als. demons.rated that a more s.atially accurate vulnerability analys.s.is.more cons.rvative too. For ins.ance, zones.with high-ris. levels.decreas.d by 42.8% when the s.udy s.ale moved from the block to the zone level of analys.s. s.milarly, areas.with low ris. increas.d by 80%. In comparis.n to previous.s.udies. our findings.s.ow that ts.nami ris. in Cartagena Bay is.s.gnificantly lower if coping capacities.s.ch as.evacuation potential are included in the analys.s.

关键词： Agent-bas.d model Chile Evacuation Ris. analys.s Ts.nami