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Monitoring phagocytic uptake of amyloid beta into glial cell lysosomes in real time

Prakash, P; Jethava, KP; Korte, N; Izquierdo, P; Favuzzi, E; Rose, IVL; Guttenplan, KA; ... Chopra, G; + view all (2021) Monitoring phagocytic uptake of amyloid beta into glial cell lysosomes in real time. Chemical Science 10.1039/d1sc03486c. (In press). Green open access

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Abstract

Phagocytosis by glial cells is essential to regulate brain function during health and disease. Therapies for Alzheimer's disease (AD) have primarily focused on targeting antibodies to amyloid β (Aβ) or inhibitng enzymes that make it, and while removal of Aβ by phagocytosis is protective early in AD it remains poorly understood. Impaired phagocytic function of glial cells during later stages of AD likely contributes to worsened disease outcome, but the underlying mechanisms of how this occurs remain unknown. We have developed a human Aβ_{1-42} analogue (Aβ^{pH}) that exhibits green fluorescence upon internalization into the acidic organelles of cells but is non-fluorescent at physiological pH. This allowed us to image, for the first time, glial uptake of Aβ^{pH} in real time in live animals. We find that microglia phagocytose more AβpH than astrocytes in culture, in brain slices and in vivo. Aβ^{pH} can be used to investigate the phagocytic mechanisms responsible for removing Aβ from the extracellular space, and thus could become a useful tool to study Aβ clearance at different stages of AD.

Type: Article
Title: Monitoring phagocytic uptake of amyloid beta into glial cell lysosomes in real time
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/d1sc03486c
Publisher version: https://doi.org/10.1039/D1SC03486C
Language: English
Additional information: © Royal Society of Chemistry 2021. This article is Open Access (http://creativecommons.org/licenses/by/3.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10132654
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