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Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2

Journal of Molecular Cell Biology 2014年第4期8卷 299-311页

作者： Lucia Garcia-Guerra Rocio Vila-Bedmar marta carrasco-rando marta Cruces-Sande Mercedes Martin Ana Ruiz-Gomez Mar Ruiz-Gomez Margarita Lorenzo Sonia Fernandez-Veledo Federico Mayor Jr. Cristina Murga Iria Nieto-Vazquez Department of Biochemistry and Molecular Biology II School of Pharmacy Complutense University 28040 Madrid Spain CIBER de Diabetes y Enfermedades Metab61icas Asociadas (CIBERDEM) 08017 Barcelona Spain Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM) 28029 Madrid Spain CIBER de enfermedades neurodegenerativas (CIBERNED) 28049 Madrid Spain Departament of Molecular Biology and Centro de Biologia Molecular Severo Ochoa (CSIC-UAM) 28049 Madrid Spain Instituto de Investigacion Sanitaria la Princesa 28006 Madrid Spain Centro de Biologia Molecular Severo Ochoa (UAM-CSIC) 28049 Madrid Spain Hospital Universitari de Tarragona Joan XXIII. IISPV. Universitat Rovira i Virgili 43007 Tarragona Spain

G protein-coupled receptor kinase 2 （GRK2） is an important serine/threonine-kinase regulating different membrane receptors and intraceUular proteins. Attenuation of Drosophila Gprk2 in embryos or adult flies induced a defective differentiation of somatic muscles, loss of fibers, and a flightless phenotype. In vertebrates, GRK2 hemizygous mice contained less but more hypertrophied skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts, overexpression of a GRK2 kinase-deficient mutant （K220R） caused precocious differentiation of ceUs into immature myotubes, which were wider in size and contained more fused nuclei, while GRK2 overexpression blunted differentiation. Moreover, p38MAPK and Akt pathways were activated at an earlier stage and to a greater extent in K220R-expressing cells or upon kinase downregulation, while the activation of both kinases was impaired in GRK2-overexpressing cells. The impaired differentiation and fewer fusion events promoted by enhanced GRK2 levels were recapitulated by a p38MAPK mutant, which was able to mimic the inhibitory phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation observed in GRK2-expressing clones was rescued in the presence of a constitutively active upstream stimulator of the p38MAPK pathway. These results suggest that balanced GRK2 function is necessary for a timely and complete myogenic process.

关键词： GRK2 p38MAPK Akt skeletal muscle myogenesis

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The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni marta Busnelli Silvia Bassani CNR Institute of Neuroscience Vedano al LambroItaly NeuroMi Milan Center for Neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： marta Chierichetti Riccardo Cristofani Valeria Crippa Veronica Ferrari marta Cozzi Elena Casarotto Paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores 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 SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Not only myelination: the immune-inflammatory functions of oligodendrocytes

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Neural Regeneration Research 2022年第12期17卷 2661-2663页

作者： marta Boccazzi Stefano Raffaele marta Fumagalli Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilanItaly

Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve *** formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of *** addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS *** their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.

关键词： myelin cytes homeostasis

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Evolution of temperature indices in the periglacial environment of the European Alps in the period 1990-2019

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Journal of Mountain Science 2021年第11期18卷 2842-2853页

作者： NIGRELLI Guido CHIARLE marta National Research Council Research Institute for Geo-hydrological ProtectionStrada delle Cacce73–TorinoItaly

Air temperature in the European Alps shows warming over recent decades at an average rate of 0.3℃/10 years,therebyoutpacing the global warming rate of 0.2℃/10 *** periglacial environment of the Alps is particularly important for several aspects(*** production,tourism,natural hazards,indicator of global warming).However,there is a lack of specific and updated studies relating to temperature change in this *** order to fill this gap,the recent temperature trends in the periglacial environment of the Alps were ***/maximum/minimum daily air temperatures recorded by 14 land-based meteorological stations were used,and the temperature indices for the period 1990-2019 were *** periglacial environment of the Alps showed a warming rate of 0.4℃/10 years,0.6℃/10 years and 0.8℃/10 years for the mean/maximum/minimum temperatures,*** warming rates are higher than that observed for the entire Alpine *** 2050 many glaciers of the Alps below 3000 m altitude are expected to be extinct,and all the areas previously occupied by glaciers will become *** order to manage and adapt to these changes,more in-depth climate analyses are *** is necessary for all the mountainous areas of the world,which are undergoing similar changes.

关键词： Mountain climate Cryosphere Climate change Extreme temperature Air temperature trend

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1991-2020 climate normal in the European Alps:focus on high-elevation environments

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Journal of Mountain Science 2023年第8期20卷 2149-2163页

作者： NIGRELLI Guido CHIARLE marta Istituto di Ricerca per la Protezione Idrogeologica Consiglio Nazionale delle RicercheTorino 10135Italy

Alps are an important geographical area of the European continent and,in this area,temperature increase is most ***,the 1991-2020 climate normal in the Alps has still not been thoroughly *** to fill this gap with a focus on high-elevation environments,minimum and maximum daily air temperature acquired by 23 automatic weather station were *** results show that the mean annual values of minimum and maximum temperature for the 1991-2020 climate normal in the Alps are-2.4℃ and 4.4℃,respectively,with a warming rate of 0.5℃/10 *** mean annual temperature comparison between 1961-1990 and 1971-2000,1961-1990 and 1981-2010,1961-1990 and 1991-2020 climate normal show an increase of 0.3℃,0.5℃ and 0.9℃,*** results also confirm that seasonal and annual temperatures are rising through the whole Alpine arc,mainly in summer and *** work highlights that annual minimum and maximum temperature do not seem to be affected by a positive elevation-dependent ***,a positive elevation-dependent warming in the maximum values of the annual minimum temperature was *** anthropogenic emissions maintain the trend of the last decades,the expected mean annual temperature of the 2001-2030 climate normal is-0.2℃,with an increase of 0.5℃ if compared to the 1991-2020 climate normal and with an increase of 1.5℃ if compared to the 1961-1990 climate *** study highlights the warming rate that is now present in the European Alps,provides indications on the warming rate that will occur in the coming years and highlights the importance of carrying out investigations that consider not only the last 30-year climate normal,but also the most recent 30-year climate normal by comparing them with each other.

关键词： Air temperature trend Climate normal Climate change High mountain climate Alps

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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa Roade Mar Riveiro-Barciela Adriana Palom Francisco Rodríguez-Frías marta Bes Ariadna rando María Teresa Salcedo Rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda Rafael Esteban María Buti Liver Unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Liver Pathology Lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de Recerca(VHIR) Liver Diseases GroupBarcelonaSpain Transfusion Safety Laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their *** aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their ***-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative ***,analytical,and virological data were collected,and a liver biopsy was performed if *** were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap ***:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray ***-nine(25.9%)individuals re-quired a liver *** HBV DNA hazard ratio(HR)6.0,p<0.001),HBV core-related antigen(HBcrAg)(HR 6.5,p<0.001),and elastography(HR 4.6,p<0.001)were inde-pendently associated with the IC *** ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUROC)of 0.925(95%CI:0.880-0.970,p<0.001)for identification of *** AUROC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/*** ACE score of<1 had a positive predictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier Liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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