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  1. Artikel ; Online: Editorial

    Huinan Li / Laralynne Przybyla / Joel W. Blanchard

    Frontiers in Cell and Developmental Biology, Vol

    Understanding human biology with iPSC derived cell types in the Era of CRISPR technology

    2023  Band 11

    Schlagwörter CRISPR ; genome editing ; IPSC ; stem cell ; CRISPR screen ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Understanding LRRK2 kinase activity in preclinical models and human subjects through quantitative analysis of LRRK2 and pT73 Rab10

    Xiang Wang / Elvira Negrou / Michael T. Maloney / Vitaliy V. Bondar / Shan V. Andrews / Manuel Montalban / Ceyda Llapashtica / Romeo Maciuca / Hoang Nguyen / Hilda Solanoy / Annie Arguello / Laralynne Przybyla / Nathan J. Moerke / Sarah Huntwork-Rodriguez / Anastasia G. Henry

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Band 17

    Abstract: Abstract Variants in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with increased risk for familial and sporadic Parkinson’s disease (PD). Pathogenic variants in LRRK2, including the common variant G2019S, result in increased LRRK2 kinase ... ...

    Abstract Abstract Variants in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with increased risk for familial and sporadic Parkinson’s disease (PD). Pathogenic variants in LRRK2, including the common variant G2019S, result in increased LRRK2 kinase activity, supporting the therapeutic potential of LRRK2 kinase inhibitors for PD. To better understand the role of LRRK2 in disease and to support the clinical development of LRRK2 inhibitors, quantitative and high-throughput assays to measure LRRK2 levels and activity are needed. We developed and applied such assays to measure the levels of LRRK2 as well as the phosphorylation of LRRK2 itself or one of its substrates, Rab10 (pT73 Rab10). We observed increased LRRK2 activity in various cellular models of disease, including iPSC-derived microglia, as well as in human subjects carrying the disease-linked variant LRRK2 G2019S. Capitalizing on the high-throughput and sensitive nature of these assays, we detected a significant reduction in LRRK2 activity in subjects carrying missense variants in LRRK2 associated with reduced disease risk. Finally, we optimized these assays to enable analysis of LRRK2 activity following inhibition in human peripheral blood mononuclear cells (PBMCs) and whole blood, demonstrating their potential utility as biomarkers to assess changes in LRRK2 expression and activity in the clinic.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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