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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)

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development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

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Neural Regeneration Research 2021年第1期16卷 16-20页

作者： Guadalupe Álvarez-Hernán José Antonio de Mera-Rodríguez yolanda Gañán Jorge Solana-Fajardo Gervasio Martín-Partido Joaquín Rodríguez-León Javier Francisco-Morcillo Área de biología celular Departamento de AnatomíaBiología Celular y ZoologíaFacultad de CienciasUniversidad de ExtremaduraBadajozSpain Área de Anatomía Humana Departamento de AnatomíaBiología Celular y ZoologíaFacultad de MedicinaUniversidad de ExtremaduraBadajozSpain Servicio de Oftalmología Complejo Hospitalario Universitario de BadajozBadajozSpain

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in *** vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller *** proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very *** region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal ***,regenerative response after injury occurs with low efficiency in the precocial avian *** contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at *** particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear ***,stem cell niches are very active in the retina of altricial *** more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.

关键词： altricial birds circumferential marginal zone Müller glia postnatal neurogenesis precocial regeneration retinogenesis

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Exocytosis,endocytosis and recycling of secretory vesicles in neuroendocrine cells,and its regulation by cortical actin

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BIOCELL 2022年第8期46卷 1867-1873页

作者： ANA M.CÁRdeNAS I.GALLO FERNANDO D.MARENGO Centro Interdisciplinario de Neurociencia de Valparaíso Facultad de CienciasUniversidad de ValparaísoValparaíso2360102Chile Instituto de Fisiología Biología Molecular y NeurocienciasCONICET.Departamento de Fisiología y Biología Molecular y CelularFacultad de Ciencias Exactas y Naturales Universidad de Buenos AiresBuenos Aires1428Argentina

The cortical actin network is a mesh of filaments distributed beneath the plasmalemma that dynamically reacts in response to *** dynamic network of cortical filaments,together with motor myosin partners,adjusts the plasmalemma tension,organizes membrane protein microdomains,remodels the cell surface and drives vesicle motion in order to fine-tune exocytosis,endocytosis and recycling of secretory *** this review,we discuss how these mechanisms work in secretory cells.

关键词： Cortical actin Neuroendocrine cell Chromaffin cell Exocytosis Endocytosis

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The combination of a microbial and a non-microbial biostimulant increases yield in lettuce(Lactuca sativa) under salt stress conditions by up-regulating cytokinin biosynthesis

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Journal of Integrative Plant biology 2024年第10期66卷 2140-2157页

作者： Patricia Benito Marina Celdrán Javier Bellón Vicente Arbona Miguel González-Guzmán Rosa Porcel Lynne yenush José M.Mulet Instituto de biología Molecular y celular de Plantas(IBMCP) Universitat Politècnica de València-Consejo Superior de Investigaciones CientíficasValencia 46022Spain Caldic Ibérica S.L.Barcelona 08210Spain department of biología Bioquímica y Ciencias NaturalesUniversitat Jaume ICampus Riu SecE-Castellón 12071Spain

Salinization poses a significant challenge in agriculture, exacerbated by anthropogenic global warming. Biostimulants, derived from living microorganisms or natural extracts, have emerged as valuable tools for conventional and organic ***, our understanding of the molecular mechanisms underlying the effects of biostimulants is very limited, especially in crops under real cultivation conditions. In this study, we adopted an integrative approach to investigate the effectiveness of the combined application of plant growth-promoting bacterium(Bacillus megaterium strain BM08) and a non-microbial biostimulant under control conditions(normal watering) and salt stress. After confirming the yield increase under both conditions, we investigated the molecular mechanisms underlying the observed effect by measuring a number of physiological parameters(i.e., lipid peroxidation, antioxidants,chlorophylls, total phenolics and phytohormone content), as well as RNA sequencing and primary metabolite analyses. Our findings reveal that the combined effect of the microbial and non-microbial biostimulants led to a decrease in the antioxidant response and an up-regulation of genes involved in cytokinin biosynthesis under salt stress ***, in turn, resulted in a higher concentration of the bioactive cytokinin, isopentenyladenosine, in roots and leaves and an increase in γ-aminobutyric acid, a non-proteic amino acid related to abiotic stress responses. In addition, we observed a decrease in malic acid, along with an abscisic acid(ABA)-independent up-regulation of SR-kinases, a family of protein kinases associated with abiotic stress responses. Furthermore, we observed that the single application of the non-microbial biostimulant triggers an ABA-dependent response under salt stress;however, when combined with the microbial biostimulant, it potentiated the mechanisms triggered by the BM08 bacterial strain. This comprehensive investigation shows that the combination o

关键词： abscisic acid biostimulants cytokinins isopentenyl adenosine lettuce salt stress

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Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases

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Neural Regeneration Research 2020年第9期15卷 1631-1638页

作者： Kevin Puertas-Neyra Ricardo Usategui-Martín Rosa MCoco Ivan Fernandez-Bueno Instituto Universitario de Oftalmobiologia Aplicada Universidad de ValladolidValladolidSpain Centro en Red de Medicina Regenerativa y Terapia celular de Castilla y Leon ValladolidSpain Red Tematica de Investigacion Cooperativa en Salud OftaredInstituto de Salud CarlosⅢValladolidSpain

Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.

关键词： clinical trials growth factors intraocular injection intravitreal injection neuroprotection paracrine properties photoreceptors preclinical models retinal diseases stem cells

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Neuroprotective therapy for retinal neurodegenerative diseases by stem cell secretome

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Neural Regeneration Research 2021年第1期16卷 117-118页

作者： Ricardo Usategui-Martín Ivan Fernandez-Bueno Instituto Universitario de Oftalmobiología Aplicada(IOBA) Retina GroupUniversidad de ValladolidValladolidSpain Centro en Red de Medicina Regenerativa y Terapia celular de Castilla y León Red Temática de Investigación Cooperativa en SaludOftaredInstituto de Salud Carlos IIIValladolidSpain

Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness *** had been estimated that the prevalence of these diseases varies between 1/750 and 1/5000 depending on the region,the level of consanguinity or ethnicity(Na et al.,2017).The functional and structural complexity of the retina makes it susceptible to multiple types of pathogenic damage.

关键词： diseases protective degenerative

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Lens Capsule HSPG-Perlecan Regulates Lens Fibre Differentiation during Chick Embryo development

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Open Journal of Veterinary Medicine 2017年第2期7卷 9-22页

作者： Cristina Martín María I. Alonso Francisco Lamus José A. Moro A. de la Mano José M. Fernandez Alberto Caballero ángel Gato departamento de Anatomía y Radiología Laboratorio de Desarrollo y Teratología del Sistema Nervioso. Instituto de Neurociencias de Castilla y León (INCYL) Facultad de Medicina Universidad de Valladolid Valladolid Espa&#241a departamento de biología celular Histología y Farmacología Facultad de Medicina Universidad de Valladolid Valladolid Spain

Lens fibre differentiation is a life-long process related with lens transparency, and is particularly intense during development, being related with an FGF-2 antero-posterior gradient at the equator level as the main growth factor involved which has been related with the basal membrane of the lens anlagen known as “Lens capsule”. However the lens fibre differentiation induced by FGF2 depends, as in other biological systems, on the local bioavailability of FGF-2 regulated by their relationship with extracellular matrix molecules as Heparan Sulphate Proteoglycans. Here, we try to clarify how Perlecan (a heparan sulphate proteoglycan specific from basement membranes) is involved in lens fibre differentiation at earliest stages of eye development. Our results show that Perlecan, is a major component in the lens capsule during the earliest stages of lens development in chick embryos being present during lens plate induction, lens vesicle stage and the onset of lens fibre differentiation. In order to demonstrate a direct involvement of HSPG-Perlecan in lens fibre differentiation, we generate depleted lenses by HSPG-Perlecan synthesis disruption and specific enzymatic digestion. The HSPG-Perlecan depleted lens show a significant delay or abolition in the lens fibre differentiation which remains in an immature cells displaying DNA synthesis in the posterior epithelium and a decrease in FGF2 lens expression. These data support the hypothesis that lens capsule HSPG-Perlecan is a key molecule involved in lens fibre differentiation during development, probably by involvement in FGF-2 biodisponibility.

关键词： Eye development Lens Fibre Differentiation HSPG-Perlecan FGF-2 Chick Embryo

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New insights on the molecular mechanisms of collateral sprouting after peripheral nerve injury

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Neural Regeneration Research 2021年第9期16卷 1760-1761页

作者： Dominique Lemaitre Felipe A.Court Universidad del desarrollo Facultad de MedicinaCentro de Fisiología Celular e IntegrativaSantiagoChile Center for Integrative biology Faculty of SciencesUniversidad MayorSantiagoChile Geroscience Center for Brain Health and Metabolism(GERO) SantiagoChile The Buck Institute for Research on Aging NovatoCAUSA

Axonal regeneration after injuries to the nervous system has been extensively studied due to its implication in motor and sensory functional recovery. Distinct types of regeneration has been identified, such as canonical axonal regeneration, defined as the growth of axons from the transected axonal stump to reinnervate the original target, or regenerative sprouting, in which the growth occurs from a region of the damaged axon either close or far from the injury site(Tuszynski and Steward, 2012).

关键词： injuries injury collateral

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David García-Bernal Diego García-Ayuso Manuel Vidal-Sanz Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical *** stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and *** studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional ***,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous ***,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Mesenchymal stromal cell therapy for damaged retinal ganglion cells, is gold all that glitters?

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Neural Regeneration Research 2019年第11期14卷 1851-1857页

作者： Fernando Lucas-Ruiz Caridad Galindo-Romero David García-Bernal María Norte-Munoz Kristy T. Rodríguez-Ramírez Manuel Salinas-Navarro Jose E. Millán-Rivero Manuel Vidal-Sanz Marta Agudo-Barriuso Grupo de Oftalmologia Experimental Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain department of Talmologia Universidad de MurciaMurciaSpain Unidad de Terapia celular y Trasplante Hematopoyetico Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain department of Medicina Interna Universidad de MurciaMurciaSpain

Mesenchymal stromal cells are an excellent source of stem cells because they are isolated from adult tissues or perinatal derivatives, avoiding the ethical concerns that encumber embryonic stem cells. In preclinical models, it has been shown that mesenchymal stromal cells have neuroprotective and immunomodulatory properties, both of which are ideal for central nervous system treatment and repair. Here we will review the current literature on mesenchymal stromal cells, focusing on bone marrow mesenchymal stromal cells, adipose-derived mesenchymal stromal cells and mesenchymal stromal cells from the umbilical cord stroma, i.e.,Wharton’s jelly mesenchymal stromal cells. Finally, we will discuss the use of these cells to alleviate retinal ganglion cell degeneration following axonal trauma.

关键词： stem cells adipose stem cells umbilical cord bone marrow Wharton's jelly optic nerve axotomy neuroprotection

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