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Olfactory receptors in neural regeneration in the central nervous system

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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Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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Neural Regeneration research 2024年第9期19卷 1967-1972页

作者： Laura Carrero DesireéAntequera Cristina Municio Eva Carro Group of neurodegenerative diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic ***,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional ***,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： Alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

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Neuronal circuitry reconstruction after stem cell therapy in damaged brain

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Neural Regeneration research 2022年第9期17卷 1959-1960页

作者： Daniel Tornero Department of biomedical Sciences Institute of Neuroscience and Production and Validation Center of Advanced Therapies(Creatio)University of Barcelona August Pi I Sunyer biomedical research Institute(IDIBAPS) network center for biomedical research in neurodegenerative diseases(ciberned) BarcelonaSpain

Transplantation of neuronal precursors derived from human pluripotent stem cells is a promising therapy for the treatment of neurological disorders associated with neuronal loss,such us neurodegenerative diseases,brain trauma and *** functional integration of grafted neurons differentiated from stem cells into the host injured neuronal circuitry has been a major challenge in cell therapy strategies for brain repair(Palma-Tortosa et al.,2021).Even though other cell types or mechanisms may provide modest clinical improvements,neuronal replacement and reconstruction of the damaged area are crucial for an optimal and long-term recovery.

关键词： diseases damaged

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Implication of salivary lactoferrin and periodontal-mediated infections in Alzheimer's disease

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Neural Regeneration research 2023年第12期18卷 2691-2692页

作者： Cristina Municio Eva Carro Group of neurodegenerative diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neurobiology of Alzheimer’s disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)Instituto de Salud Carlos IIIMadridSpain

Lactoferrin is an antimicrobial prote in characterized by the exertion of many protective functions,including antibacterial,antifungal,antiviral,and antiparasitic properties,as well as anti-inflammatory and immunomodulatory activities(Kruzel et al.,2017).Lactoferrin is one of the major proteins present in exocrine secretions,including saliva,and is therefore associated with host defense against oral pathogens and control of the oral *** recent years,it has become clear that alterations in the oral microbiome may contribute to opportunistic pathogen infections in the brains of Alzheimer’s disease(AD)patients and thus participate in or contribute to the development of this neurodegenerative disease(Sureda et al.,2020).Pathogenic oral microbes can affect neurological processes by entering brain tissue through various pathways and directly damaging the central nervous *** the central nervous system,oral microbes may trigger an immune response that increases amyloidβ(Aβ)production and may even trigger the Aβcascade to promote the onset of AD,as we discuss in our previous study supporting the“infectious hypothesis”in AD(González-Sánchez et al.,2020).

关键词： Alzheimer infections protective

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Cerebrospinal fluid neurogranin as a new player in prion disease diagnosis and prognosis

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Neural Regeneration research 2020年第5期15卷 861-862页

作者： Anna Villar-Piqué Inga Zerr Franc Llorens network center for biomedical research in neurodegenerative diseases (ciberned) Institute Carlos IIIMinistry of HealthHospitalet de LlobregatSpain Bellvitge biomedical research Institute (IDIBELL) Hospitalet de LlobregatSpain Department of Neurology Clinical Dementia Center and National Reference Center for CJD SurveillanceUniversity Medical SchoolGotingenGermany German center for neurodegenerative diseases (DZNE) GotingenGermany

Neurogranin (Ng) and its role as Alzheimer’s disease (AD) biomarker: Ng is a calmodulin-binding protein mainly expressed in cerebral structures such as the cortex,hippocampus and *** is mainly located in the dendritic processes,particularly in post-synaptic compartments,but also in the cytosolic compartment,being likely involved in the regulation of the intracellular calcium-calmodulin signaling pathway (Represa et al.,1990).In the last decade,a plethora of studies have demonstrated that cerebrospinal fluid (CSF) Ng is increased in AD patients and in individuals with an ADlike CSF profile (Kester et al.,2015a).This increase seems to be disease-specific because other neurodegenerative conditions including frontotemporal dementia,Lewy body dementia,Parkinson’s disease,progressive supranuclear palsy,multiple system atrophy or Huntington’s disease,present CSF Ng concentrations similar to controls (Wellington et al.,2016).Ng levels in CSF appear to be elevated in mild cognitive impairment (MCI)-affected individuals who progress to AD and are highly related to memory and cognitive function (Kester et al.,2015a;Tarawneh et al.,2016),which indicates that this protein may serve as an early AD biomarker with diagnostic utility in pre-dementia disease stages,and with prognostic utility to predict cognitive decline and MCI-to-AD conversion.

关键词： Represa cerebrospinal fluid multiple system

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Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1-40 and cerebral vulnerability in normal aging

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Translational Neurodegeneration 2019年第1期8卷 423-432页

作者： Marta Manzano-Crespo Mercedes Atienza Jose L.Cantero Laboratory of Functional Neuroscience Pablo de Olavide UniversityCtra.de Utrera Km 141013 SevilleSpain ciberned Network Center for Biomedical Research in Neurodegenerative Diseases28031MadridSpain

Background:Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β(Aβ)deposition and chronic cerebral hypoperfusion,both factors largely associated with the development of ***,reduced 2-[18F]fluoro-2-deoxy-D-glucose(FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of *** on this evidence,we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly ***:Ninety-five normal elderly subjects underwent clinical,cognitive,structural MRI,and FDG-PET *** expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this *** analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning,plasma Aβ,structural and metabolic brain ***:Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ1–40,deficits in cortical glucose metabolism,and volume reduction of the entorhinal *** significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical ***:These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.

关键词： Aging Alzheimer’s disease Blood biomarkers microRNAs Amyloid-beta FDG-PET Entorhinal cortex

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Aquaporin 5 in Alzheimer’s disease:a link between oral and brain pathology?

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Neural Regeneration research 2023年第7期18卷 1491-1492页

作者： Cristina Municio Eva Carro Group of neurodegenerative diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain network center for biomedical research in neurodegenerative diseases(ciberned) Instituto de Salud Carlos IIIMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain

The involvement of aquaporins(AQPs)in the development of diseases has been widely described(Azad et al.,2021).AQP5 has been described in astrocytes changing after traumatic brain injuries(Chai et al.,2013),but the precise role of AQP5 in Alzheimer’s disease(AD)pathology is yet to be *** have recently reported that AQP5 expression changes during the development of AD(Antequera et al.,2022).The AQP5 expression in salivary glands is decreased in 6-month-old APP/PS1 mice and AD *** decrease in AQP5 expression could be involved in the mechanism of salivary gland dysfunction described in a previous study(Antequera et al.,2021).Now,we propose a new indirect role of AQP5 in the connection between infection-induced oral dysbiosis and AD(Sureda et al.,2020).Here,we suggest that the proinflammatory response induced by oral pathogen infection results in the downregulation of AQP5 contributing to the salivary gland secretory *** these alterations destabilize the peripheral immune-inflammatory balance and exacerbate neuroinflammation and neurodegeneration leading to AD pathology.

关键词： salivary pathology Alzheimer

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Melatonin:a multitasking indoleamine to modulate hippocampal neurogenesis

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Neural Regeneration research 2023年第3期18卷 503-505页

作者： Alejandro Romero JoséÁngel Morales-García Eva Ramos Department of Pharmacology and Toxicology Faculty of Veterinary MedicineComplutense University of Madrid Institute for biomedical research“A.Sols”(CSIC-UAM) Spanish center for networked biomedical research on neurodegenerative diseases(ciberned Department of Cellular Biology School of MedicineComplutense University of MadridMadridSpain

Neurodegeneration affects a large number of cell types including neurons,astrocytes or oligodendrocytes,and neural stem *** stem cells can generate new neuronal populations through proliferation,migration,and *** neurogenic potential may be a relevant factor to fight neurodegeneration and *** the last years,we can find growing evidence suggesting that melatonin may be a potential modulator of adult hippocampal *** lack of therapeutic strategies targeting neurogenesis led researchers to explore new *** preclinical studies with melatonin observed how melatonin can modulate and enhance molecular and signaling pathways involved in *** made a special focus on the connection between these modulation mechanisms and their implication in neurodegeneration,to summarize the current knowledge and highlight the therapeutic potential of melatonin.

关键词： adult hippocampal neurogenesis aging melatonin neural stem cell neurodegeneration neuroprotection signaling pathway therapeutic strategy

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Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease:removing axonal debris

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Translational Neurodegeneration 2021年第4期10卷 554-572页

作者： Ingrid Morales Ricardo Puertas-Avendaño Alberto Sanchez Adrian Perez-Barreto Clara Rodriguez-Sabate Manuel Rodriguez Laboratory of Neurobiology and Experimental Neurology Department of Basic Medical SciencesFaculty of MedicineLa Laguna UniversityLa LagunaTenerifeCanary IslandsSpain center for networked biomedical research on neurodegenerative diseases(ciberned) MadridSpain

Objective:The dopaminergic nigrostriatal neurons(DA cells)in healthy people present a slow degeneration with aging,which produces cellular debris throughout *** 2%-5%of people present rapid cell degeneration of more than 50%of DA cells,which produces Parkinson's disease(PD).Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells,particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic *** synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation,this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells,paying particular attention to the relative roles of astrocytes and ***:Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine,inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage,microgliosis or *** possible retrograde degeneration of dopaminergic axons,and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy ***:The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain *** spheroids retained mitochondria and most(e.g.,tyrosine hydroxylase,the dopamine transporter protein,and amyloid precursor protein)but not all(e.g.,α-synuclein)proteins of the degenerating dopaminergic *** showed initial(autophagosomes)but not late(lysosomes)components of autophagy(incomplete autophagy).These spheroids were penetrated by astrocytic processes of the medial forebrain bundle,which provided the lysosomes needed to continue the degradation of dopaminergic debri

关键词： Astrocyte Phagocytosis Parkinson's disease Dying-back degeneration Medial forebrain bundle Spheroid

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Neuronal chemokines:new insights into neuronal communication after injury

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Neural Regeneration research 2023年第11期18卷 2379-2380页

作者： Francina Mesquida-Veny Arnau Hervera Molecular and Cellular Neurobiotechnology Institute for Bioengineering of Catalonia(IBEC)BarcelonaSpain Department of Cell Biology Physiology and ImmunologyUniversity of BarcelonaBarcelonaSpain network Centre of biomedical research of neurodegenerative diseases(ciberned) Institute of Health Carlos ⅢMinistry of Economy and CompetitivenessMadridSpain Institute of Neuroscience University of BarcelonaBarcelonaSpain

Classically,chemokines were described as small proteins driving leukocyte ***,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neural *** the last years,research has highlighted the importance of chemokines in the nervous system,governing a wide range of processes (MesquidaVeny et al.,2021).This is evidenced for example by the crucial role played by CXCL12 during cortical development,or the homeostatic role of neuronal CX3CL1,preventing microglial *** are now certain that many chemokines and their receptors are widely expressed in neurons,and growing evidence has shown them as fundamental players in direct neuronal communication,both during homeostasis and after insult.

关键词： CXCL12 chemokine

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