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Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta department of Pharmaceutical sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra institute for health Research(IdiSNA) PamplonaSpain

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.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin Thomas Nystrom institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden department of Life sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

Brain age estimation:premise,promise,and problems

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Neural Regeneration Research 2025年第8期20卷 2313-2314页

作者： Jarrad Perron Ji Hyun Ko Graduate Program in Biomedical Engineering Price Faculty of EngineeringUniversity of ManitobaWinnipegMBCanada PrairieNeuro Research Centre Kleysen Institute for Advanced MedicineHealth Sciences CentreWinnipegMBCanada department of Human Anatomy and Cell Science Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada

Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North *** old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.

关键词： estimation providing birth

Gut microbiota in cancer initiation,development and therapy

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Science China Life sciences 2025年

作者： Ruyi Zhang Xiang Zhang Harry Cheuk Hay Lau Jun Yu institute of Digestive Disease and department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong Kong

Cancer has long been associated with genetic and environmental factors,but recent studies reveal the important role of gut microbiota in its initiation and *** 13%of cancers are linked to infectious agents,highlighting the need to identify the specific microorganisms *** microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune *** can lead to cancer,while certain probiotics and their metabolites may help reestablish microecological balance and improve anti-tumor immune *** into targeted approaches that enhance therapy with probiotics is ***,the effects of probiotics in humans are complex and not yet fully ***,methods to counteract harmful bacteria are still in *** clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer *** research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the health sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1699-1700页

作者： Seyed Mojtaba Hosseini Soheila Karimi-Abdolrezaee department of Physiology and Pathophysiology Spinal Cord Research CentreRady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada Manitoba Multiple Sclerosis Research Center WinnipegMBCanada Children Hospital Research institute of Manitoba WinnipegMBCanada

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

关键词： peroxidation Fischer injury

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University institute of Cardiovascular sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University health Science Centre Peking University department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 139-158页

作者： Fengjuan Jiao Lingyan Meng Kang Du Xuezhi Li School of Mental health Jining Medical UniversityJiningShandong ProvinceChina Shandong Collaborative Innovation Center for Diagnosis Treatment and Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandong ProvinceChina

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in *** one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these *** evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s ***,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome ***,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s *** this review,we briefly introduce the machinery of ***,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome ***,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

关键词： autophagy chemical therapy gene therapy Parkinson’s disease α-synuclein

Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

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Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang Stephen Temitayo Bello department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for Regenerative Medicine and health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator