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  1. Article: Detection and Functional Evaluation of the P2X7 Receptor in hiPSC Derived Neurons and Microglia-Like Cells.

    Francistiová, Linda / Vörös, Kinga / Lovász, Zsófia / Dinnyés, András / Kobolák, Julianna

    Frontiers in molecular neuroscience

    2022  Volume 14, Page(s) 793769

    Abstract: A large body of evidence suggests the involvement of the ATP-gated purinergic receptor P2X7 (P2X7R) in neurodegenerative diseases, including Alzheimer's disease. While it is well-described to be present and functional on microglia cells contributing to ... ...

    Abstract A large body of evidence suggests the involvement of the ATP-gated purinergic receptor P2X7 (P2X7R) in neurodegenerative diseases, including Alzheimer's disease. While it is well-described to be present and functional on microglia cells contributing to inflammatory responses, some reports suggest a neuronal expression of the receptor as well. Here, we present experimental results showing P2X7 receptors to be expressed on human hiPSC-derived microglia-like cells, hiPSC-derived neuronal progenitors and hiPSC-derived matured neuronal cells. By applying cell surface protein detection assays, we show that P2X7R is not localized on the cell membrane, despite being detected in neuronal cells and thus may not be available for directly mediating neurotoxicity. On hiPSC-derived microglia-like cells, a clear membranous expression was detected. Additionally, we have not observed differences in P2X7R functions between control and familial Alzheimer's disease patient-derived neuronal cells. Functional assays employing a P2X7R antagonist JNJ 47965567 confirm these findings by showing P2X7R-dependent modulation of microglia-like cells viability upon treatment with P2X7R agonists ATP and BzATP, while the same effect was absent from neuronal cells. Since the majority of P2X7R research was done on rodent models, our work on human hiPSC-derived cells presents a valuable contribution to the field, extending the work on animal models to the human cellular system and toward clinical translation.
    Language English
    Publishing date 2022-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2021.793769
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain.

    Francistiová, Linda / Klepe, Adrián / Curley, Géza / Gulya, Károly / Dinnyés, András / Filkor, Kata

    Frontiers in immunology

    2021  Volume 12, Page(s) 730088

    Abstract: In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the ... ...

    Abstract In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients' mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus' neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.
    MeSH term(s) COVID-19/complications ; COVID-19/immunology ; Central Nervous System Infections/complications ; Central Nervous System Infections/virology ; Cytokine Release Syndrome/complications ; Cytokine Release Syndrome/immunology ; Humans ; Lung/immunology ; Lung/virology ; Microglia/immunology ; Microglia/pathology ; Microglia/virology ; Nervous System Diseases/virology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity
    Language English
    Publishing date 2021-08-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.730088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Role of P2X7 Receptor in Alzheimer's Disease.

    Francistiová, Linda / Bianchi, Carolina / Di Lauro, Caterina / Sebastián-Serrano, Álvaro / de Diego-García, Laura / Kobolák, Julianna / Dinnyés, András / Díaz-Hernández, Miguel

    Frontiers in molecular neuroscience

    2020  Volume 13, Page(s) 94

    Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by a progressive cognitive decline associated with global brain damage. Initially, intracellular paired helical filaments composed by hyperphosphorylated tau and ... ...

    Abstract Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by a progressive cognitive decline associated with global brain damage. Initially, intracellular paired helical filaments composed by hyperphosphorylated tau and extracellular deposits of amyloid-β (Aβ) were postulated as the causing factors of the synaptic dysfunction, neuroinflammation, oxidative stress, and neuronal death, detected in AD patients. Therefore, the vast majority of clinical trials were focused on targeting Aβ and tau directly, but no effective treatment has been reported so far. Consequently, only palliative treatments are currently available for AD patients. Over recent years, several studies have suggested the involvement of the purinergic receptor P2X7 (P2X7R), a plasma membrane ionotropic ATP-gated receptor, in the AD brain pathology. In this line, altered expression levels and function of P2X7R were found both in AD patients and AD mouse models. Consequently, genetic depletion or pharmacological inhibition of P2X7R ameliorated the hallmarks and symptoms of different AD mouse models. In this review, we provide an overview of the current knowledge about the role of the P2X7R in AD.
    Language English
    Publishing date 2020-06-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2020.00094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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