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

Autor: Prakash P; Department of Chemistry, Purdue University West Lafayette IN 47907 USA gchopra@purdue.edu., Jethava KP; Department of Chemistry, Purdue University West Lafayette IN 47907 USA gchopra@purdue.edu., Korte N; Department of Neuroscience, Physiology and Pharmacology, University College London London WC1E 6BT UK., Izquierdo P; Department of Neuroscience, Physiology and Pharmacology, University College London London WC1E 6BT UK., Favuzzi E; Department of Neurobiology, Harvard Medical School 220 Longwood Avenue Boston MA 02115 USA.; Stanley Center at the Broad 75 Ames Street Cambridge MA 02142 USA., Rose IVL; Neuroscience Institute, NYU Grossman School of Medicine New York NY 10016 USA., Guttenplan KA; Department of Neurobiology, Stanford University Stanford CA 94305 USA., Manchanda P; Department of Chemistry, Purdue University West Lafayette IN 47907 USA gchopra@purdue.edu., Dutta S; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University West Lafayette IN 47907 USA., Rochet JC; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University West Lafayette IN 47907 USA.; Purdue Institute for Integrative Neuroscience, Purdue University West Lafayette IN 47907 USA., Fishell G; Department of Neurobiology, Harvard Medical School 220 Longwood Avenue Boston MA 02115 USA.; Stanley Center at the Broad 75 Ames Street Cambridge MA 02142 USA., Liddelow SA; Neuroscience Institute, NYU Grossman School of Medicine New York NY 10016 USA.; Department of Neuroscience & Physiology, NYU Grossman School of Medicine New York NY 10016 USA.; Department of Ophthalmology, NYU Grossman School of Medicine New York NY 10016 USA., Attwell D; Department of Neuroscience, Physiology and Pharmacology, University College London London WC1E 6BT UK., Chopra G; Department of Chemistry, Purdue University West Lafayette IN 47907 USA gchopra@purdue.edu.; Purdue Institute for Integrative Neuroscience, Purdue University West Lafayette IN 47907 USA.; Purdue Institute for Drug Discovery 720 Clinic Drive West Lafayette IN 47907 USA.; Purdue Center for Cancer Research, Purdue University West Lafayette IN 47907 USA.; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University West Lafayette IN 47907 USA.
Jazyk: angličtina
Zdroj: Chemical science [Chem Sci] 2021 Jul 21; Vol. 12 (32), pp. 10901-10918. Date of Electronic Publication: 2021 Jul 21 (Print Publication: 2021).
DOI: 10.1039/d1sc03486c
Abstrakt: 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 Aβ pH 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.
Competing Interests: Shane Liddelow is an academic founder of AstronauTx Ltd. Other authors declare no competing financial interests.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
Externí odkaz: