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Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis

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Translational Neurodegeneration 2023年第1期12卷 722-744页

作者： Cristina de Dios Xenia Abadin Vicente Roca-Agujetas Marina Jimenez-Martinez albert morales Ramon Trullas Montserrat Mari Anna Colell Department of Cell Death and Proliferation Institut d’Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas(CSIC)Institut d’Investigacions Biomèdiques August Pi I Sunyer(IDIBAPS)BarcelonaSpain Centro de Investigación Biomédica en Red Sobre Enferme-dades Neurodegenerativas(CIBERNED) MadridSpain Department of Biomedicine Faculty of MedicineUniversitat de BarcelonaBarcelonaSpain Present Address:Department of Biochemistry and Molecular Biology Faculty of PharmacyUniversidad de Sevilla.Instituto de Biomedicina de Sevilla(IBiS)-Hospital Universitario Virgen del Rocío/CSICSevilleSpain Present Address:Department of Clinical Immunology and Rheumatology Amsterdam UMCAmsterdamNetherlands

Background Persistent inflammatory response in the brain can lead to tissue damage and *** Alzheimer’s disease(AD),there is an aberrant activation of inflammasomes,molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D(GSDMD),the executor of ***,the mechanisms underlying the sustained activation of inflammasomes in AD are largely *** have previously shown that high brain cholesterol levels promote amyloid-β(Aβ)accumulation and oxidative ***,we investigate whether these cholesterol-mediated changes may regulate the inflam-masome *** SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-soluble cholesterol *** exposure to lipopolysaccharide(LPS)plus muramyl dipeptide or Aβ,activation of the inflammasome pathway was analyzed by immunofluorescence,ELISA and immunoblotting ***-labeled Aβwas employed to monitor changes in microglia *** medium was used to study how microglia-neuron interrelationship modulates the inflammasome-mediated *** In activated microglia,cholesterol enrichment promoted the release of encapsulated IL-1βaccompanied by a switch to a more neuroprotective phenotype,with increased phagocytic capacity and release of neurotrophic *** contrast,in SH-SY5Y cells,high cholesterol levels stimulated inflammasome assembly triggered by both bacterial toxins and Aβpeptides,resulting in GSDMD-mediated ***(GSH)ethyl ester treatment,which recovered the cholesterol-mediated depletion of mitochondrial GSH levels,significantly reduced the Aβ-induced oxidative stress in the neuronal cells,resulting in lower inflammasome activation and cell ***,using conditioned media,we showed that neuronal pyroptosis affects the function of the cholesterol-enriched microglia,lowering its phagocytic activity and,the

关键词： Neuroinflammation Mitochondrial oxidative stress Phagocytosis Alzheimer’s disease DAM signature NLRP3

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Boosting third-harmonic generation by a mirror-enhanced anapole resonator

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Light(Science & Applications) 2018年第1期7卷 661-668页

作者： Lei Xu Mohsen Rahmani Khosro Zangeneh Kamali Aristeidis Lamprianidis Lavinia Ghirardini Jürgen Sautter Rocio Camacho-morales Haitao Chen Matthew Parry Isabelle Staude Guoquan Zhang Dragomir Neshev Andrey E.Miroshnichenko School of Engineering and Information Technology University of New South WalesCanberraACT 2600Australia Nonlinear Physics Centre The Australian National UniversityCanberraACT 2601Australia Department of Physics Politecnico di MilanoPiazza Leonardo Da Vinci 3220133 MilanItaly Institute of Applied Physics Abbe Center of PhotonicsFriedrich Schiller University JenaAlbert-Einstein-Str.1507745 JenaGermany The MOE Key Laboratory of Weak Light Nonlinear Photonics School of Physics and TEDA Applied Physics InstituteNankai UniversityTianjin 300457China

We demonstrate that a dielectric anapole resonator on a metallic mirror can enhance the third harmonic emission by two orders of magnitude compared to a typical anapole resonator on an insulator *** employing a gold mirror under a silicon nanodisk,we introduce a novel characteristic of the anapole mode through the spatial overlap of resonantly excited Cartesian electric and toroidal dipole *** is a remarkable improvement on the early demonstrations of the anapole mode in which the electric and toroidal modes interfere ***,our system produces a significant near-field enhancement,facilitating the nonlinear ***,the mirror surface boosts the nonlinear emission via the free-charge oscillations within the interface,equivalent to producing a mirror image of the nonlinear source and the pump beneath the *** found that these improvements result in an extremely high experimentally obtained efficiency of 0.01%.

关键词： resonator pump mirror

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