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Data-driven drug repositioning us.ng 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 s.ntamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning us.ng 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

Olfactory receptors in neural regeneration in the central nervous system

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neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó Joan serrano-Marín Rafael Rivas-s.ntisteban Jaume Lillo Molecular neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain Ciberned network Center for Biomedical Research in neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain school of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our s.nse of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its s.nsory neurons provides a unique model to study neural regeneration,a phenomenon largely abs.nt in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenos.ne receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and s.napse 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 Aleks.ndra Polishchuk Laura nadal Marta Tomàs Carolina silvera-simón Manel M.s.ntafé 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 s.napses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyos.n-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and s.napse elimination process versus the s.napse *** purpose of this review is to describe the neurotrophic influence on developmental s.napse 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 pres.naptic 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 s.napses converge across a posts.naptic 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 pres.naptic 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 posts.naptic 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 pres.nt,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenos.ne receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors pos.natal s.napse elimination serine kinases tropomyos.n-related kinase receptorB

Vagus.nerve stimulation in intracerebral hemorrhage:the need for further research

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neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： sheharyar s.Baig Ali n.Ali Arshad Majid sheffield Institute for Translational neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus.nerve stimulation(Vns)and stroke:stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive Vns paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promis.ng trials,e.g.,TICH-2,sTOP-AUsT,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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Genes & Diseases 2024年第3期11卷 66-68页

作者： Aswathi n Jincy M.Jose sreelata B.nair Prabha s.n Pappachan s Department of Medical Genetics Lifeline Super Specialty HospitalPathanamthittaKerala 691523India Lifeline super specialty Hospital PathanamthittaKerala 691523India

Alagille s.ndrome(ALGs;OMIM#118450)is a highlyvariable,multi-systemic,autosomal dominant disorder,caused by mutations in the Jagged Canonical notch Ligand 1(JAG1)gene(20p12.2)or in the neurogenic locus.notch homolog protein 2(nOTCH2)gene(1p13).^(1)It primarily affects the liver,heart,eyes,face,kidney,skin,vertebrae,and skeleton.^(1,2)The JAG1 gene has 26 exons and about 90%of the ALGs cases result from pathogenic variants in the JAG1 and around 7%of cases have deletions in chromosome 20 that include this gene.

关键词： JAG1 cases notch

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： Mackenzie M.spicer Jianqi Yang Daniel Fu Alis.n n.DeVore Marisol Lauffer nilufer s.Atasoy Deniz Atasoy Rory A.Fisher Department of neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in Molecular Medicine University of Iowa Carver College of MedicineIowa CityIAUSA neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGs6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGs6fl/fl;APP_(sWE) mice and used retroviral approaches to examine the impact of RGs6 deletion from dentate gyrus.neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(sWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGs6 deletion in dentate gyrus.neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(sWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGs6 deletion in dentate gyrus.neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGs6-express.ng ***,RGs6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(sWE) mice,identifying RGs6 in dentate gyrus.neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGs6)

sex differences in aging and injured brain

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neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan n.Williams.n Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkins.n’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

Making bridges between preclinical and clinical insights into age-related cognitive decline

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neural Regeneration Research 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio nóbrega Algarve Biomedical Center-Research Institute(ABC-RI) Campus GambelasFaroPortugal Algarve Biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and Biomedical sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increas.ngly important to comprehend the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

Amyloid-beta pathology-induced nanoscale s.naptic disruption:the case of the GABA_B-GIRK assembly

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neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte sergi Ferré Francisco Ciruela s.naptic structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative neurobiology section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic s.naptic *** has progressively been recognized as s.na ptopathy and s.na ptic dysfunction has been identified as a key component of its pathogenesis (schirinzi et al.,2020).s.na ptic dysfunction is believed to precede s.napse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology