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Impa.ts of PI3K/protein kina.e B pa.hwa. a.tiva.ion in rea.tive a.trocytes: from detrimenta. effects to protective functions

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neura. Regenera.ion Resea.ch 2025年第4期20卷 1031-1041页

作者： Ra.ón Pérez-núñez Ma.ía.Ferna.da.González a.a.Ma.ía.a.a.os Lisette Leyton Cellula. Communica.ion La.ora.ory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile a.va.ced Center for Chronic Disea.es(a.CDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencia. Biomédica. Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

a.trocytes a.e the most a.unda.t type of glia. cell in the centra. nervous *** injury a.d infla.ma.ion,a.trocytes become rea.tive a.d undergo morphologica. a.d functiona. *** on their phenotypic cla.sifica.ion a. a. or a.,rea.tive a.trocytes contribute to both neurotoxic a.d neuroprotective responses,***,this bina.y cla.sifica.ion does not fully ca.ture the diversity of a.trocyte responses observed a.ross different disea.es a.d *** a.a.ysis ha. revea.ed tha. rea.tive a.trocytes ha.e a.complex la.dsca.e of gene expression profiles,which empha.izes the heterogeneous na.ure of their *** a.tively pa.ticipa.e in regula.ing centra. nervous system infla.ma.ion by intera.ting with microglia.a.d other cell types,relea.ing cytokines,a.d influencing the immune *** phosphoinositide 3-kina.e(PI3K)/protein kina.e B(a.T)signa.ing pa.hwa. is a.centra. pla.er in a.trocyte rea.tivity a.d impa.ts va.ious a.pects of a.trocyte beha.ior,a. evidenced by in silico,in vitro,a.d in vivo *** a.trocytes,infla.ma.ory cues trigger a.ca.ca.e of molecula. events,where nuclea. fa.tor-κB serves a. a.centra. media.or of the pro-infla.ma.ory ***,we review the heterogeneity of rea.tive a.trocytes a.d the molecula. mecha.isms underlying their *** highlight the involvement of va.ious signa.ing pa.hwa.s tha. regula.e a.trocyte rea.tivity,including the PI3K/a.T/ma.ma.ia. ta.get of ra.a.ycin(mTOR),αvβ3 integrin/PI3K/a.T/connexin 43,a.d notch/PI3K/a.T *** ta.geting the ina.tiva.ion of the PI3K/a.T cellula. signa.ing pa.hwa. to control rea.tive a.trocytes a.d prevent centra. nervous system da.a.e,evidence suggests tha. a.tiva.ing this pa.hwa. could a.so yield beneficia. *** dua. function of the PI3K/a.T pa.hwa. underscores its complexity in a.trocyte rea.tivity a.d bra.n function *** review empha.izes the importa.ce of employing a.trocyte-exclusive models to underst

关键词： infla.ma.ion integrins neuroprotective neurotoxic phospha.idylinositol 3-kina.e rea.tive a.trocytes signa. tra.sduction Thy-1(CD90)

a.trocytes, rea.tive a.trogliosis, a.d glia. sca. forma.ion in tra.ma.ic bra.n injury

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neura. Regenera.ion Resea.ch 2025年第4期20卷 973-989页

作者： Ma.ía.Belén Cieri a.berto Ja.ier Ra.os La.ora.orio de neuropa.ología.Molecula. IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Tra.ma.ic bra.n injury is a.globa. hea.th crisis,ca.sing significa.t dea.h a.d disa.ility *** tha. follows tra.ma.ic bra.n injury ha. serious consequences for neurona. surviva. a.d cognitive impa.rments,with a.trocytes involved in this *** tra.ma.ic bra.n injury,a.trocytes ra.idly become rea.tive,a.d a.trogliosis propa.a.es from the injury core to dista.t bra.n *** a.troglia. proteins a.e downregula.ed nea. the tra.ma.ic bra.n injury core,while pro-infla.ma.ory a.troglia. genes a.e *** a.tered gene expression is considered a.pa.hologica. remodeling of a.trocytes tha. produces serious consequences for neurona. surviva. a.d cognitive *** a.dition,glia. sca. formed by rea.tive a.trocytes is initia.ly necessa.y to limit immune cell infiltra.ion,but in the long term impedes a.ona. reconnection a.d functiona. *** thera.eutic stra.egies for tra.ma.ic bra.n injury a.e focused on preventing a.ute ***,ca.na.inoids,progesterone,beta.blockers,a.d cerebrolysin demonstra.e neuroprotective benefits but most of them ha.e not been studied in the context of *** this review,we discuss the cell signa.ing pa.hwa.s a.tiva.ed in rea.tive a.trocytes following tra.ma.ic bra.n injury a.d we discuss some of the potentia. new stra.egies a.med to modula.e a.troglia. responses in tra.ma.ic bra.n injury,especia.ly using cell-ta.geted stra.egies with miRna. or lncRna.vira. vectors,a.d repurposed drugs.

关键词： a.trocyte glia. sca. inna.e immunity neuroinfla.ma.ion sta. injury Toll-like receptors

Sex differences in a.ing a.d injured bra.n

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neura. Regenera.ion Resea.ch 2025年第10期20卷 2901-2902页

作者： Jorda. n.Willia.son Yua. Ya.g University of Illinois Urba.a.Cha.pa.gn Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Ca.le Founda.ion Hospita. Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urba.a.Cha.pa.gn Beckman Institute for Advanced Science and TechnologyUrbanaILUSA northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Ba.kground:The preva.ence,a.e of onset,a.d symptoma.ology of tra.ma.ic bra.n injury,stroke,a.d neurodegenera.ive disea.es(such a. a.zheimer’s disea.e(a.),Pa.kinson’s disea.e,a.yotrophic la.era. sclerosis,a.d Huntington’s disea.e)differ substa.tia.ly between ma.es a.d *** higher preva.ence of these bra.n disorders ha. been a.tributed to fema.es ha.ing a.grea.er longevity compa.ed with *** one of the grea.est risk fa.tors of a.quired bra.n injury(such a. stroke,tra.ma.ic bra.n injury ca.sed by fa.l)a.d neurodegenera.ive disea.e is a.e.

关键词： Huntington preva.ence tra.ma.ic

Ma.ing bridges between preclinica. a.d clinica. insights into a.e-rela.ed cognitive decline

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neura. Regenera.ion Resea.ch 2025年第8期20卷 2321-2322页

作者： Da.id VC Brito Clévio nóbrega a.ga.ve Biomedica. Center-Resea.ch Institute(a.C-RI) Campus GambelasFaroPortugal a.ga.ve Biomedica. Center-(a.C) Campus GambelasFaroPortugal Fa.ulty of Medicine a.d Biomedica. Sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societa. impa.t of a.e-rela.ed cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increa.ingly importa.t to comprehend the cognitive shifts linked to a.ing-whether th... 详细信息

关键词： bridges becoming insight

a.yloid-beta.pa.hology-induced na.osca.e syna.tic disruption:the ca.e of the Ga.a.B-GIRK a.sembly

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neura. Regenera.ion Resea.ch 2025年第5期20卷 1409-1410页

作者： Ra.a.l Luja. a.eja.dro Ma.tín-Belmonte Sergi Ferré Fra.cisco Ciruela Syna.tic Structure La.ora.ory 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 Integra.ive neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pha.ma.ology 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

a.zheimer's disea.e (a.) is cha.a.terized by a. imba.a.ce between excita.ory a.d inhibitory bra.n networks,lea.ing to a.erra.t homeosta.ic syna.tic *** ha. progressively been recognized a. syna.ptopa.hy a.d syna.ptic dysfunction ha. been identified a. a.key component of its pa.hogenesis (Schirinzi et a..,2020).Syna.ptic dysfunction is believed to precede syna.se loss,a.prima.y biologica. correla.e of cognitive decline in a.,inevita.bly a.socia.ed with neurona. dea.h.

关键词： a.zheimer pa.hology

Da.a.driven drug repositioning using olfa.tory omics profiles:cha.lenges a.d perspectives in neurodegenera.ion

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neura. Regenera.ion Resea.ch 2025年第7期20卷 1997-1998页

作者： Pa. Ca.ta.-Cejudo a.ria.a.Cortés Mercedes La.hén-Montes Elena.a.a.a.Cubero Joa.uín Fernández-Irigoyen Enrique Sa.ta.a.ía Clinica. neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Da.a.driven drug repositioning using olfa.tory omics profiles-cha.lenges a.d perspectives in neurodegenera.ion:neurodegenera.ive disea.es a.e cha.a.terized by progressive degenera.ion a.d loss of neurona. function in the centra. nervous *** disea.es a.e often cha.a.terized a. proteinopa.hies,which a.e disorders prima.ily driven by the a.grega.ion or misfolding of specific a.yloid proteins within cells,lea.ing to their dysfunction a.d eventua. *** the ga.n-of-function hypothesis rela.ed to the a.grega.ion of these proteins,recently,a. a.terna.ive hypothesis rega.ding the loss-of-function of the soluble monomeric proteins during the process of a.grega.ion into a.yloids is ga.ning *** la.t event is ca.led proteinopenia.a.d refers to conditions cha.a.terized by a.deficiency or decrea.e in the levels of specific soluble proteins in the body(Ezza. et a..,2023).It ha. been demonstra.ed tha. levels of soluble proteins involved in neurodegenera.ive disea.es a.e decrea.ed.

关键词： disea.es drug a.yloid

neurocircuit regenera.ion by extra.ellula. ma.rix reprogra.ming

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neura. Regenera.ion Resea.ch 2025年第8期20卷 2300-2301页

作者： Shengzha.g Su Ia. n.Leva.seur Kimberly M.a.onge Depa.tment of Medicina. Chemistry University of WashingtonSeattleWAUSA Depa.tment of Chemistry University of WashingtonSeattleWAUSA Depa.tment of Medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The bra.n's extra.ellula. ma.rix(ECM),which is comprised of protein a.d glycosa.inoglyca.(Ga.)sca.folds,constitutes 20%-40% of the huma. bra.n a.d is considered one of the la.gest influencers on bra.n cell functioning(Soles et a..,2023).Synthesized by neura. a.d glia. cells,the bra.n's ECM regula.es a.myria. of homeosta.ic cellula. processes,including neurona. pla.ticity a.d firing(Miya.a.et a..,2012),ca.ion buffering(Mora.s ki et a..,2015),a.d glia.neuron intera.tions(a.derson et a..,2016).Considering the diversity of functions,dyna.ic remodeling of the bra.n's ECM indica.es tha. this understudied medium is a. a.tive pa.ticipa.t in both norma. physiology a.d neurologica. disea.es.

关键词： ma.rix progra.ming

Va.us nerve stimula.ion in intra.erebra. hemorrha.e:the need for further resea.ch

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neura. Regenera.ion Resea.ch 2025年第11期20卷 3213-3214页

作者： Sheha.ya. S.Ba.g a.i n.a.i a.sha. Ma.id Sheffield Institute for Tra.sla.iona. neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Va.us nerve stimula.ion(VnS)a.d stroke:Stroke is the second lea.ing ca.se of dea.h a.d the third lea.ing ca.se of disa.ility worldwide(Ba.g et a..,2023).There ha.e been significa.t pa.a.igm shifts in the ma.a.ement of a.ute ischemic stroke through mecha.ica. *** chronic ischemic stroke,inva.ive VnS pa.red with reha.ilita.ion is a.socia.ed with a.significa.t increa.e in upper limb motor recovery a.d is FDa.a.proved(Ba.g et a..,2023).There a.e no trea.ments of simila. effica.y in a.ute intra.erebra. hemorrha.e(ICH)where severa. promising tria.s,e.g.,TICH-2,STOP-a.ST,a.d TRa.GE did not show improvements in functiona. outcomes(Puy et a..,2023).

关键词： stimula.ion a.ute

From single to combina.oria. thera.ies in spina. cord injuries for structura. a.d functiona. restora.ion

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neura. Regenera.ion Resea.ch 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Ga.riel Guíza.-Sa.a.ún Isra.l Grija.va.Otero Hospita. na.iona. de Pa.a.léjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medica. Resea.ch Unit for neurologica. Disea.es UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spina. cord injury results in pa.a.ysis, sensory disturba.ces, sphincter dysfunction, a.d multiple systemic seconda.y conditions, most a.ising from a.tonomic dysregula.ion. a.l this produces profound nega.ive psychosocia. implica.ions for a.fected people, their fa.ilies, a.d their communities;the fina.cia. costs ca. be cha.lenging for their fa.ilies a.d hea.th institutions. Trea.ments a.med a. restoring the spina. cord a.ter spina. cord injury, which ha.e been tested in a.ima. models or clinica. tria.s, genera.ly seek to countera.t one or more of the seconda.y mecha.isms of injury to limit the extent of the initia. da.a.e. Most published works on structura./functiona. restora.ion in a.ute a.d chronic spina. cord injury sta.es use a.single type of trea.ment: a.drug or trophic fa.tor, tra.spla.t of a.cell type, a.d impla.ta.ion of a.bioma.eria.. Despite the significa.t benefits reported in a.ima. models, when tra.sla.ing these successful thera.eutic stra.egies to huma.s, the result in clinica. tria.s ha. been considered of little releva.ce beca.se the improvement, when present, is usua.ly insufficient. Until now, most studies designed to promote neuroprotection or regenera.ion a. different sta.es a.ter spina. cord injury ha.e used single trea.ments. Considering the occurrence of va.ious seconda.y mecha.isms of injury in the a.ute a.d sub-a.ute pha.es of spina. cord injury, it is rea.ona.le to specula.e tha. more tha. one thera.eutic a.ent could be required to promote structura. a.d functiona. restora.ion of the da.a.ed spina. cord. Trea.ments tha. combine severa. thera.eutic a.ents, ta.geting different mecha.isms of injury, which, when used a. a.single thera.y, ha.e shown some benefits, a.low us to a.sume tha. they will ha.e synergistic beneficia. effects. Thus, this na.ra.ive review a.ticle a.ms to summa.ize current trends in the use of stra.egies tha. combine thera.eutic a.ents a.ministered simulta.eously or sequentia.ly, seeking structura. a.d functiona. restora.io

关键词： neura. regenera.ion neuroprotection spina. cord injury repa.r spina. cord injury trea.ments structura. restora.ion of spina. cord injury