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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： ramón Pérez-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 reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity 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 review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,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 reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

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

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 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 repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease 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 decreased.

关键词： diseases drug amyloid

The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2243-2264页

作者： Edgar Pérez-Herrero Alberto fernández-Medarde Departamento de Ingeniería Química y Tecnología Farmacéutica Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Bio-Orgánica Antonio González Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Tecnologías Biomédicas Universidad de La LagunaLa Laguna 38200TenerifeSpain Instituto de Biología Molecular y Celular Del Cáncer Centro de Investigación Del Cáncer(USAL-CSIC)Salamanca 37007Spain

Solid tumors are complex entities,comprising a wide variety of malignancies with very different molecular *** this,they share a set of characteristics known as"hallmarks of cancer"that can be used as common therapeutic ***,every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates,and these adaptations lead to alterations in extra-and intracellular *** changes in p H are common to all solid tumors,and can be used either as therapeutic targets,blocking the cell proton transporters and reversing the pH changes,or as means to specifically deliver anticancer *** this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic *** will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light ***,we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery,describing how nanocarriers are being used to increase drug stability and specificity.

关键词： pH-Gradient inversion Metabolism of glucose Proton transport inhibitors Proton-caged carriers Chemotherapy Targeted drug delivery pH-Sensitive nanocarriers Warburg effect Cancer

Retinal microglial activation in glaucoma:evolution over time in a unilateral ocular hypertension model

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Neural Regeneration Research 2022年第4期17卷 797-799页

作者： JoséA.fernández-Albarral Ana I.ramírez Rosa de Hoz Juan J.Salazar Instituto de Investigaciones Oftalmológicas ramón Castroviejo Universidad Complutense de MadridMadridSpain Facultad deÓptica y Optometría Departamento de InmunologíaOftalmología y ORLUniversidad Complutense de MadridMadridSpain

Glaucoma is a neurodegenerative chronic pathology,characterized by the loss of retinal ganglion cells(RGC),which leads to an irreversible vision field *** increased intraocular pressure(IOP)constitutes its main risk ***,the main treatments for glaucoma are focused on decreasing IOP;nevertheless,the progression of the disease continues,despite IOP *** fact shows the existence of other factors that could contribute to the advance of glaucomatous *** early diagnostics,the use of neuroprotective therapies,and knowledge of the pathological processes are the major challenges associated with the management of this *** pathogenic mechanisms have been proposed to be responsible for RGC death,including oxidative stress,mitochondrial dysfunction,glutamate excitotoxicity,and neuroinflammation(Casson et al.,2012).

关键词： irreversible oxidative activation

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative Medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi Department of Veterinary Sciences University of TurinGrugliascoTOItaly Department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

The versatility of Fe(Ⅱ) in the synthesis of uniform citrate-stabilized plasmonic nanoparticles with tunable size at room temperature

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Nano Research 2020年第9期13卷 2351-2355页

作者： Carlos fernández-Lodeiro Javier fernández-Lodeiro Enrique Carbó-Argibay Carlos Lodeiro Jorge Pérez-Juste Isabel Pastoriza-Santos CINBIO Universidade de VigoCampus universitario LagoasMarcosende36310 VigoSpain Galicia Sur Health Research Institute(IIS Galicia Sur) SERGAS-UVIGO36312 VigoSpain BIOSCOPE Group LAQV@REQUIMTEChemistry DepartmentNOVA School of Science and TechnologyNOVA University LisbonCaparica Campus2829-516 CaparicaPortugal PROTEOMASS Scientific Society Rua dos InventoresMadam ParqueCaparica Campus2829-516 CaparicaPortugal International Iberian Nanotechnology Laboratory(INL) Av.Mestre Jose Veiga s/n4715-330 BragaPortugal

A highly versatile seed-mediated approach for the synthesis of citrate-stabilized gold,silver and palladium nanoparticles(NPs)with size control is *** use of iron(Ⅱ)as a reducing agent enables the fabrication of monodisperse NPs in a wide range of sizes(from 15 nm to at least 120 nm(90 nm for Pd))at room *** citrate as capping ligand on the NPs surface facilitates its further surface modification with proteins and thiolated molecules.

关键词： plasmonic nanoparticles gold silver palladium citrate-stabilized Fe(Ⅱ)

Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández fernado García-Dolores Humberto Nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(INCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

ON A CLASS OF RIEMANN SURFACES

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Analysis in Theory and Applications 2006年第4期22卷 377-386页

作者： Arturo fernández Javier Pérez Ciudad Universitaria Spain

It is considered the class of Riemann surfaces with dimT1=0, where T1 is a subclass of exactharmonic forms which is one of the factors in the orthogonal decomposition of the space Ω^H of harmonic forms of the surface, namely Ω^H=＊Ω^H＋T1＋＊T0^H＋T0^H＋T2The surfaces in the class OHD and the clase of planar surfaces satisfy dimT1 =0. *** posed the question whether there might exist other surfaces outside those two classes. Here it is shown that in the case of finite genus g, we should look for a surface S with dimTl = 0 among the surfaces of the form Sg／K , where Sg is a closed surface of genus g and K a compact set of positive harmonic measure with perfect components and very irregular boundary.

关键词： Harmonic form orthogonal decomposition Diriehlet norm