A Screen of Plant-Based Natural Products Revealed That Quercetin Prevents Pyroglutamylated Amyloid-β (Aβ3(pE)-42) Uptake in Astrocytes As Well As Resulting Astrogliosis and Synaptic Dysfunction.

Autor: Arndt H; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany., Bachurski M; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany., Yuanxiang P; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany., Franke K; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, 06108, Halle, Germany.; Institute of Biology/Geobotany and Botanical Garden, Martin Luther University Halle-Wittenberg, 06108, Halle, Germany.; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103, Leipzig, Germany., Wessjohann LA; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, 06108, Halle, Germany.; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103, Leipzig, Germany.; Institut Für Chemie, Chair of Natural Products Chemistry, Martin-Luther-University Halle-Wittenberg, 06120, Halle (Saale), Germany., Kreutz MR; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany. Michael.Kreutz@lin-magdeburg.de.; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany. Michael.Kreutz@lin-magdeburg.de.; German Center for Neurodegenerative Diseases (DZNE), 39120, Magdeburg, Germany. Michael.Kreutz@lin-magdeburg.de.; Center for Behavioral Brain Sciences, Otto Von Guericke University, 39120, Magdeburg, Germany. Michael.Kreutz@lin-magdeburg.de., Grochowska KM; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany. Katarzyna.Grochowska@zmnh.uni-hamburg.de.; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany. Katarzyna.Grochowska@zmnh.uni-hamburg.de.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Sep 25. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1007/s12035-024-04509-6
Abstrakt: Two connected histopathological hallmarks of Alzheimer's disease (AD) are chronic neuroinflammation and synaptic dysfunction. The accumulation of the most prevalent posttranslationally modified form of Aβ1-42, pyroglutamylated amyloid-β (Aβ3(pE)-42) in astrocytes is directly linked to glial activation and the release of proinflammatory cytokines that in turn contribute to early synaptic dysfunction in AD. At present, the mechanisms of Aβ3(pE)-42 uptake to astrocytes are unknown and pharmacological interventions that interfere with this process are not available. Here we developed a simple screening assay to identify substances from a plant extract library that prevent astroglial Aβ3(pE)-42 uptake. We first show that this approach yields valid and reproducible results. Second, we show endocytosis of Aβ3(pE)-42 oligomers by astrocytes and that quercetin, a plant flavonol, is effective to specifically block astrocytic buildup of oligomeric Aβ3(pE)-42. Importantly, quercetin does not induce a general impairment of endocytosis. However, it efficiently protects against early synaptic dysfunction following exogenous Aβ3(pE)-42 application.
(© 2024. The Author(s).)
Databáze: MEDLINE
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