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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano sergei A.Kirov jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain ramón y Cajal Institute for Health Research(IRYCIs) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of neuroscience and Regenerative Medicine&department of neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(l-alanine,glycine,l-glutamine,and l-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by n-methyl-D-aspartate *** n-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system n transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through n-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling n-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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nucleoside modified mRnA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal nógrádi department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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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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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-santisteban 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 sense 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 sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent 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： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Data-driven drug repositioning using 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 santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using 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

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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 promising 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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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： leyre Ayerra Maria s.Aymerich Universidad de navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de navarra PamplonaSpain IdisnA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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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 Alison 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-expressing ***,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)

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Do Rules and Patterns Affect design Maintainability?

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Journal of Computer science & Technology 2009年第2期24卷 262-272页

作者： Javier Garzás félix García Mario Piattini Kybele Consulting Madrid Spain Department of Information Technologies and Systems-Escuela Superior de Informáica University of Castilla-La Mancha Alarcos Research Group-Institute of Information Technologies and systems department of Information Technologies and systems-Escuela superior de Informáica University of Castilla-la Mancha

At the present time, best rules and patterns have reached a zenith in popularity and diffusion, thanks to the software community＇s efforts to discover, classify and spread knowledge concerning all types of rules and patterns. Rules and patterns are useful elements, but many features remain to be studied if we wish to apply them in a rational manner. The improvement in quality that rules and patterns can inject into design is a key issue to be analyzed, so a complete body of empirical knowledge dealing with this is therefore necessary. This paper tackles the question of whether design rules and patterns can help to improve the extent to which designs are easy to understand and modify. An empirical study, composed of one experiment and a replica, was conducted with the aim of validating our conjecture. The results suggest that the use of rules and patterns affect the understandability and modifiability of the design, as the diagrams with rules and patterns are more difficult to understand than non-rule/pattern versions and more effort is required to carry out modifications to designs with rules and patterns.

关键词： design patterns and rules maintainability software quality object-oriented design

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software Vulnerabilities Overview:A descriptive study

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Tsinghua science and Technology 2020年第2期25卷 270-280页

作者： Mario Calín s.n.hez Juan Manuel Carrillo de Gea José luis fernández-Alemán jesús Garcerán Ambrosio Toval the department of Informatics and systems Faculty of Computer ScienceUniversity of Murcia

Computer security is a matter of great *** the last decade there have been numerous cases of cybercrime based on the exploitation of software *** fact has generated a great social concern and a greater importance of computer security as a *** this work,the most important vulnerabilities of recent years are identified,classified,and categorized individually.A measure of the impact of each vulnerability is used to carry out this classification,considering the number of products affected by each vulnerability,as well as its *** addition,the categories of vulnerabilities that have the greatest presence are *** on the results obtained in this study,we can understand the consequences of the most common vulnerabilities,which software products are affected,how to counteract these vulnerabilities,and what their current trend is.

关键词： descriptive study software security software vulnerabilities vulnerability databases

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