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SIRT2 as a potential new therapeutic target for Alzheimer's disease 被引量:1
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作者 Noemi Sola-Sevilla Elena Puerta 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期124-131,共8页
Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this co... Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases. 展开更多
关键词 Alzheimer's disease AMYLOID AUTOPHAGY MEMORY neurodegenerative diseases NEUROINFLAMMATION sirtuin 2 TAU
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Context-dependent role of sirtuin 2 in inflammation
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作者 NoemíSola-Sevilla Maider Garmendia-Berges +1 位作者 MCarmen Mera-Delgado Elena Puerta 《Neural Regeneration Research》 SCIE CAS 2025年第3期682-694,共13页
Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has... Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases. 展开更多
关键词 INTERFERON INFLAMMATION LIPOPOLYSACCHARIDE NEUROINFLAMMATION NLRP3 nuclear factorκB sirtuin 2
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Global prevalence and gender inequalities in at least 60 min of self-reported moderate-to-vigorous physical activity 1 or more days per week:An analysis with 707,616 adolescents
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作者 Raphael H.O.Araujo AndrúO.Werneck +13 位作者 Clarice L.Martins Luciana L.Barboza Rafael M.Tassitano Nicolas Aguilar-Farias Gilmar M.Jesus Robinson Ramírez-Véelez Riki Tesler Adewale L.Oyeyemi Ellen C.M.Silva Robert G.Weaver Mark S.Tremblay Javier Brazo-Sayavera Grégore I.Mielke Danilo R.P.Silva 《Journal of Sport and Health Science》 SCIE CAS CSCD 2024年第5期709-716,共8页
Background:Guidelines recommend that adolescents should accumulate an average of 60 min per day of moderate-to-vigorous physical activity(MVPA).However,using only this cut-off could hide important information.For inst... Background:Guidelines recommend that adolescents should accumulate an average of 60 min per day of moderate-to-vigorous physical activity(MVPA).However,using only this cut-off could hide important information.For instance,from a population-level point of view,increasing physical activity for those with no or low physical activity could provide more health benefits than increasing physical activity for those with intermediate levels.Also,including a more sensitive cut-point of≥1 days per week could be an additional strategy for identifying those with low access/opportunities for physical activity practice.Thus,the current study aims to estimate the prevalence of≥60 min of MVPA≥1 days per week among adolescents globally,and to describe any relevant gender inequalities.Methods:We used representative datasets from 146 countries/territories collected between 2003 and 2019.MVPA was self-reported.Participants were grouped into younger(≤14 years old)and older(>14 years old)adolescents.Crude Poisson regression models were used to identify the relative differences in≥60 min of MVPA≥1 days per week between boys and girls,and random-effects meta-analysis models were used to identify the pooled estimates.Analyses were stratified by country and region.Results:Approximately 80%of both younger and older adolescents reported≥60 min of MVPA≥1 days per week.This prevalence was≥94%in Europe and Central Asia and North America,while the estimates for the other regions were<77%.The prevalence of≥60 min of MVPA≥1 days per week was higher among boys than girls,with the largest differences occurring among the oldest adolescents(Prevalence ratio_(≤14y)=1.04(95%confidence interval(95%CI)):1.03-1.04)vs.Prevalence ratio_(>14y)=1.09(95%CI:1.08-1.10)).Conclusion:Approximately 8 out of 10 adolescents reported accumulating≥60 min of MVPA≥1 days per week,with notable differences between regions.Gender differences were observed in several countries,especially among the oldest adolescents.Priorities for physical activity promotion among adolescents should include increasing access/opportunities for physical activity among those who do not achieve≥60 min of MVPA≥1 days per week and reducing gender inequalities. 展开更多
关键词 Global School-based Student Health Survey Health Behaviour Among School-aged Children survey Inequality Surveillance Youth
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Olfactory proteotyping: towards the enlightenment of the neurodegeneration 被引量:1
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作者 Joaquín Fernández-Irigoyen Enrique Santamaría 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第6期979-981,共3页
Although phylogenetically ancient,the olfactory system has received less attention than other sensorial systems.However,olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases(NDs)(D... Although phylogenetically ancient,the olfactory system has received less attention than other sensorial systems.However,olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases(NDs)(Doty,2012;Attems et al.,2014),which may vary from severe smell loss(e.g.,Alzheimer’s and Parkinson’s diseases)to relatively moderate loss(e.g.,progressive supranuclear palsy)(Doty,2017).Recently,a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb(OB)during the neurodegenerative process(Attems et al.,2014;Rey et al.,2018).For instance,the double-transgenic APP/PS1 mouse model of Alzheimer’s disease(AD)develops early proteomic disturbances accompanied by a specific modulation of the focal adhesion kinase(FAK)and mitogen-activated protein kinase(MAPK)dynamics at the level of the OB,demonstrating that olfactory molecular alterations occur prior toβ-amyloid plaque appearance and memory impairments in APP/PS1 transgenic mice(Lachen-Montes et al.,2016). 展开更多
关键词 ALTHOUGH phylogenetically OLFACTORY SYSTEM considered
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LIBRA:an adaptative integrative tool for paired single-cell multi-omics data
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作者 Xabier Martinez-de-Morentin Sumeer AKhan +6 位作者 Robert Lehmann Sisi Qu Alberto Maillo Narsis AKiani Felipe Prosper Jesper Tegner David Gomez-Cabrero 《Quantitative Biology》 CSCD 2023年第3期246-259,共14页
Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is... Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is challenging.In response,bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis.It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning.Methods:We designed LIBRA,a neural network based framework,to learn translation between paired multi-omics profiles so that a shared latent space is constructed.Additionally,we implemented a variation,aLIBRA,that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks.All model parameters and evaluation metrics are made available to users with minimal user iteration.Furthermore,aLIBRA allows experienced users to implement custom configurations.The LIBRA toolbox is freely available as R and Python libraries at GitHub(TranslationalBioinformaticsUnit/LIBRA).Results:LIBRA was evaluated in eight multi-omic single-cell data-sets,including three combinations of omics.We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type(clustering)resolution in the integrated latent space.Furthermore,when assessing the predictive power across data modalities,such as predictive chromatin accessibility from gene expression,LIBRA outperforms existing tools.As expected,adaptive parameter optimization(aLIBRA)significantly boosted the performance of learning predictive models from paired data-sets.Conclusion:LIBRA is a versatile tool that performs competitively in both“integration”and“prediction”tasks based on single-cell multi-omics data.LIBRA is a data-driven robust platform that includes an adaptive learning scheme. 展开更多
关键词 SINGLE-CELL multi-omic Autoencoder auto-finetuning
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In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions 被引量:2
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作者 Ana LMartínez-López Carlos JGonzález-Navarro +2 位作者 Paula Aranaz JoséLVizmanos Juan MIrache 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第4期989-1002,共14页
The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin.These nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,disp... The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin.These nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/mg.In intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium surface.The therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose conditions.In this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NPs.This finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in worms.These effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin. 展开更多
关键词 NANOPARTICLES Oral delivery Mucus-permeating BIODISTRIBUTION INSULIN Caenorhabditis elegans ROS
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Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms 被引量:1
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作者 Iñaki Etxeberria Irene Olivera +4 位作者 Elixabet Bolaños Asunta Cirella Álvaro Teijeira Pedro Berraondo Ignacio Melero 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2020年第6期576-586,共11页
Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor... Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment strategies.In this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues.Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery. 展开更多
关键词 Adoptive cell therapy T cell engineering Cancer immunotherapy
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