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Small molecules to target tau amyloid aggregation

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Neural Regeneration Research 2024年第3期19卷 509-511页

作者： Zoe Manglano-Artuñedo Samuel Peña-Díaz Salvador Ventura institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain

Protein aggregation has been linked with many neurodegenerative diseases,such as Alzheimer’s disease(AD)or Parkinson’s *** belongs to a group of heterogeneous and incurable neurodegenerative disorders collectively known as *** comprise frontotemporal dementia,Pick’s disease,or corticobasal degeneration,among *** symptomatology varies with the specific tau protein variant involved and the affected brain region or cell ***,they share a common neuropathological hallmark-the formation of proteinaceous deposits named neurofibrillary *** tangles,primarily composed of aggregated tau(Zhang et al.,2022),disrupt normal neuronal functions,leading to cell death and cognitive decline.

关键词： tau degeneration aggregation

5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

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Neural Regeneration Research 2024年第2期19卷 302-308页

作者： Joaquín Martí-Clúa Unidad de citología e Histología.departament de Biologia Cel·lular de Fisiologia i d’Immunologia.Facultad de Biociencias.Institut de Neurociències.Universidad Autónoma de Barcelona08193 BellaterraBarcelonaSpain

The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA *** the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating *** labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and *** to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of *** may lead to false results and misinterpretation in the identification of proliferative *** this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating ***,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult *** adult neurogenesis will also be *** is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.

关键词： 5-bromo-2′-deoxyuridine adult neurogenesis human adult neurogenesis labeling pitfalls prenatal neurogenesis proliferation S-phase suturing S-phase toxicity

Radiative loss of coherence in free electrons:a long-range quantum phenomenon

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Light(Science & Applications) 2024年第2期13卷 294-301页

作者： Cruz I.Velasco Valerio Di Giulio F.Javier García de Abajo ICFO-institut de ciencies Fotoniques The Barcelona Institute of Science and Technology08860Castelldefels(Barcelona)Spain ICREA-InstitucióCatalana de Recerca i Estudis Avançats Passeig Lluís Companys 2308010BarcelonaSpain

Quantum physics rules the dynamics of small objects as they interact over microscopic length ***,quantum correlations involving macroscopic distances can be observed between entangled photons as well as in atomic gases and matter waves at low *** long-range nature of the electromagnetic coupling between charged particles and extended objects could also trigger quantum phenomena over large ***,we reveal a manifestation of quantum mechanics that involves macroscopic distances and results in a nearly complete depletion of coherence associated with which-way free-electron interference produced by electron-radiation coupling in the presence of distant extended *** is a ubiquitous effect that we illustrate through a rigorous theoretical analysis of a two-path electron beam interacting with a semi-infinite metallic plate and find the inter-path coherence to vanish proportionally to the path separation at zero temperature and exponentially at finite *** investigated regime of large distances originates in the coupling of the electron to radiative modes assisted by diffraction at material structures but without any involvement of material *** the fundamental interest of this macroscopic quantum phenomenon,our results suggest an approach to measuring the vacuum temperature and nondestructively sensing the presence of distant objects.

关键词： temperature quantum macroscopic

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

design and redesign journey of a drug for transthyretin amyloidosis

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Neural Regeneration Research 2025年第4期20卷 1096-1097页

作者： Francisca Pinheiro Salvador Ventura institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the *** hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

关键词： amyloid aggregation senile

Quantum-mechanical effects in photoluminescence from thin crystalline gold films

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Light(Science & Applications) 2024年第4期13卷 783-794页

作者： Alan R.Bowman Alvaro Rodríguez Echarri Fatemeh Kiani Fadil Iyikanat Ted V.Tsoulos Joel D.Cox Ravishankar Sundararaman F.Javier García de Abajo Giulia Tagliabue Laboratory of Nanoscience for Energy Technologies(LNET) STIÉcole Polytechnique Fédérale de Lausanne(EPFL)LausanneSwitzerland ICFO–institut de ciencies Fotoniques The Barcelona Institute of Science and TechnologyCastelldefels(Barcelona)Spain. MBI–Max-Born-institut BerlinGermany. POLIMA–Center for Polariton-driven Light–Matter Interactions University of Southern DenmarkOdense MDenmark. Danish institute for Advanced Study University of Southern DenmarkOdense MDenmark. department of materials Science&Engineering Rensselaer Polytechnic InstituteTroyNYUSA. department of Physics Applied Physicsand AstronomyRensselaer Polytechnic InstituteTroyNYUSA. ICREA–Institucio Catalana de Recerca i Estudis Avancats BarcelonaSpain

Luminescence constitutes a unique source of insight into hot carrier processes in metals,including those in plasmonic nanostructures used for sensing and energy ***,being weak in nature,metal luminescence remains poorly understood,its microscopic origin strongly debated,and its potential for unraveling nanoscale carrier dynamics largely ***,we reveal quantum-mechanical effects in the luminescence emanating from thin monocrystalline gold ***,we present experimental evidence,supported by first-principles simulations,to demonstrate its photoluminescence origin(i.e.,radiative emission from electron/hole recombination)when exciting in the interband *** model allows us to identify changes to the measured gold luminescence due to quantum-mechanical effects as the gold film thickness is ***,such effects are observable in the luminescence signal from flakes up to 40 nm in thickness,associated with the out-of-plane discreteness of the electronic band structure near the Fermi *** qualitatively reproduce the observations with first-principles modeling,thus establishing a unified description of luminescence in gold monocrystalline flakes and enabling its widespread application as a probe of carrier dynamics and light-matter interactions in this *** study paves the way for future explorations of hot carriers and charge-transfer dynamics in a multitude of material systems.

关键词： luminescence quantum crystalline

Microbial phenolic metabolites are associated with better frontal lobe cognition

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Food Science and Human Wellness 2024年

作者： Inés Domínguez-López Isabella Parilli-Moser Anna Vallverdú-Queralt Anna Tresserra-Rimbau cinta Valls-Pedret Zenaida Vázquez-Ruiz Olga Casta?er Ramon Estruch Emili Ros Rosa M.Lamuela-Raventós Lipid Clinic Endocrinology and Nutrition Service institut d'Investigacions Biomèdiques August Pi i Sunyer Hospital Clínic 08036 Barcelona Spain Unit of Cardiovascular Risk and Nutrition institut Hospital del Mar de Investigaciones Médicas (IMIM) department of Preventive Medicine and Public Health University of Navarra departament de Nutrició ciències de l'Alimentació i Gastronomía Facultat de Farmacia Universitat de Barcelon (UB) Av.de Joan XXII department of Endocrinology Hospital Clinic IDIBAPS barcelona Spain department of Internal Medicine Hospital Clinic institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS) University of barcelona ciBER Fisiopatología de la Obesidad y Nutrición (ciBEROBN) instituto de Salud Carlos III institut de Nutrició i Seguretat Alimentària (INSA) Universitat de barcelona (UB)

With increasing life expectancy， neurodegenerative diseases have become one of the leading causes of ill-health in the elderly. Preventive strategies include following healthy diets， such as the Mediterranean diet， which is particularly rich in polyphenols， bioactive compounds with neuroprotective properties. The aim of this study was to assess the association of microbial phenolic metabolites (MPM) with cognition. This cross-sectional analysis was performed with 200 participants of the PREDIMED trial (barcelona-Clinic recruitment center). A novel method based on liquid chromatography coupled to mass spectrometry was used to identify urinary MPM (protocatechuic acid， enterodiol glucuronide， enterolactone glucuronide， urolithin B glucuronide， and vanillic acid glucuronide)， and cognitive function was evaluated with neuropsychological tests. Multivariable-adjusted ordinary least squares regression was used to assess the associations between cognitive function and MPM， and a score was calculated as the weighted sum of MPM. A higher MPM score was associated with better frontal lobe function. Among individual metabolites， vanillic acid glucuronide was correlated with frontal cognitive performance. Participants with higher concentrations of vanillic acid glucuronide and urolithin B glucuronide obtained better scores in the Color Trail Test part 2. A higher score for urinary multi-MPM was associated with better frontal cognitive performance in an older Mediterranean population.

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros Ana María Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular institute Icahn School of Medicine at Mount Sinai department de Nutrició ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i ciències de l'alimentació institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de barcelona department of Internal Medicine Hospital Clínic institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of barcelona Consorcio ciBER M.P.Fisiopatología de la Obesidad y Nutrición (ciBERObn) instituto de Salud Carlos III (ISciII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) ciBER de Enfermedades Cardiovasculares (ciBERCV) 9. Hospital Universitario Clínico San Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in ***: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health ***: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%ci=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%ci=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%ci=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%ci=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%ci=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%ci=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%ci=-12.37;-5.30， P-for trend ci= -3.103;-0.64， P-for trend ci= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%ci= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， espe

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