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Impacts of pI3K/protein kinase B pathway activation in re.ctive astrocytes: from detrimental effects to protective functions

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neural re.eneration re.earch 2025年第4期20卷 1031-1041页

作者： ramón pére.-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are.the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become re.ctive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,re.ctive astrocytes contribute to both neurotoxic and neuroprotective re.ponses,***,this binary classification does not fully capture.the diversity of astrocyte re.ponses observed across differe.t diseases and *** analysis has re.ealed that re.ctive astrocytes have a complex landscape of gene expre.sion profiles,which emphasizes the heterogeneous nature.of their *** actively participate in re.ulating central nervous system inflammation by interacting with microglia and other cell types,re.easing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte re.ctivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where.nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we re.iew the heterogeneity of re.ctive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that re.ulate astrocyte re.ctivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control re.ctive astrocytes and pre.ent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscore. its complexity in astrocyte re.ctivity and brain function *** re.iew emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase re.ctive astrocytes signal transduction Thy-1(CD90)

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From single to combinatorial therapies in spinal cord injuries for structural and functional re.toration

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neural re.eneration re.earch 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pére. Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical re.earch Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury re.ults in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysre.ulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Tre.tments aimed at re.toring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more.of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional re.toration in acute and chronic spinal cord injury stages use a single type of tre.tment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits re.orted in animal models, when translating these successful therapeutic strategies to humans, the re.ult in clinical trials has been considere. of little re.evance because the improvement, when pre.ent, is usually insufficient. Until now, most studies designed to promote neuroprotection or re.eneration at differe.t stages after spinal cord injury have used single tre.tments. Considering the occurre.ce of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is re.sonable to speculate that more.than one therapeutic agent could be re.uire. to promote structural and functional re.toration of the damaged spinal cord. Tre.tments that combine several therapeutic agents, targeting differe.t mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative re.iew article aims to summarize curre.t tre.ds in the use of strategies that combine therapeutic agents administere. simultaneously or sequentially, seeking structural and functional re.toratio

关键词： neural re.eneration neuroprotection spinal cord injury re.air spinal cord injury tre.tments structural re.toration of spinal cord injury

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nucleoside modified mRnA-lipid nanoparticles as a new delivery platform for the re.air of the injure. spinal cord

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neural re.eneration re.earch 2025年第8期20卷 2311-2312页

作者： Krisztián pajer Tamás Bellák Antal nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and tre.tment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous re.eneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to re.enerate their axons,the expre.sion of growth inhibitory factors,lack or suppre.sion of proper guidance cues,and profound inflammatory re.ponses do not permit successful re.eneration(Khyeam et al.,2021).

关键词： injure. capacity modified

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Sex differe.ces in aging and injure. brain

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neural re.eneration re.earch 2025年第10期20卷 2901-2902页

作者： Jordan n.Williamson Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The pre.alence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher pre.alence of these brain disorders has been attributed to females having a gre.ter longevity compare. with *** one of the gre.test risk factors of acquire. brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington pre.alence traumatic

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Astrocytes, re.ctive astrogliosis, and glial scar formation in traumatic brain injury

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neural re.eneration re.earch 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto Javier ramos Laboratorio de neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become re.ctive,and astrogliosis propagates from the injury core.to distant brain *** astroglial proteins are.downre.ulated near the traumatic brain injury core.while pro-inflammatory astroglial genes are.*** altere. gene expre.sion is considere. a pathological re.odeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by re.ctive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal re.onnection and functional *** therapeutic strategies for traumatic brain injury are.focused on pre.enting acute ***,cannabinoids,progesterone,beta-blockers,and cere.rolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this re.iew,we discuss the cell signaling pathways activated in re.ctive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial re.ponses in traumatic brain injury,especially using cell-targeted strategies with miRnAs or lncRnA,viral vectors,and re.urposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like re.eptors

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Making bridges between pre.linical and clinical insights into age-re.ated cognitive decline

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neural re.eneration re.earch 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio nóbre.a Algarve Biomedical Center-re.earch Institute(ABC-RI) Campus GambelasFaroPortugal Algarve Biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and Biomedical Sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-re.ated cognitive decline is becoming more.pronounced(Crimmins,2015).Thus,it is incre.singly important to compre.end the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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neural re.eneration re.earch 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure.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 Section 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 disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progre.sively been re.ognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to pre.ede synapse loss,a primary biological corre.ate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Data-driven drug re.ositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural re.eneration re.earch 2025年第7期20卷 1997-1998页

作者： paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug re.ositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are.characterized by progre.sive degeneration and loss of neuronal function in the central nervous *** diseases are.often characterized as proteinopathies,which are.disorders primarily driven by the aggre.ation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis re.ated to the aggre.ation of these proteins,re.ently,an alternative hypothesis re.arding the loss-of-function of the soluble monomeric proteins during the process of aggre.ation into amyloids is gaining *** last event is called proteinopenia and re.ers to conditions characterized by a deficiency or decre.se in the levels of specific soluble proteins in the body(ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are.decre.sed.

关键词： diseases drug amyloid

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neurocircuit re.eneration by extracellular matrix re.rogramming

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neural re.eneration re.earch 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian n.Levasseur Kimberly M.Alonge Department of Medicinal Chemistry University of WashingtonSeattleWAUSA Department of Chemistry University of WashingtonSeattleWAUSA Department of Medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considere. one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM re.ulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic re.odeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

关键词： matrix programming

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMn1 delivery to corre.t all neurological and systemic perturbations

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neural re.eneration re.earch 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that re.ults in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMn1)gene was identified as the main contributing factor(Lefebvre.et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMn2,which can produce low levels(approximately 10%)of the full-length functional SMn protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMn2 copy number is used as a proxy for the pre.iction of disease severity,with higher SMn2 copy number typically being associated with re.uced severity of SMA,although this re.ationship is not absolute:some individuals with low SMn2 copy number have less severe.SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMn2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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