Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain.

Autor:	Hakim-Mishnaevski K; Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel., Flint-Brodsly N; Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel., Shklyar B; Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel., Levy-Adam F; Department of Genetics and Developmental Biology, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel., Kurant E; Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel; Department of Genetics and Developmental Biology, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel. Electronic address: ekurant@univ.haifa.ac.il.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Nov 05; Vol. 29 (6), pp. 1438-1448.e3.
DOI:	10.1016/j.celrep.2019.09.086
Abstrakt:	Glial phagocytosis is critical for the development and maintenance of the CNS in vertebrates and flies and relies on the function of phagocytic receptors to remove apoptotic cells and debris. Glial phagocytic ability declines with age, which correlates with neuronal dysfunction, suggesting that increased glial phagocytosis may prevent neurodegeneration. Contradicting this hypothesis, we provide experimental evidence showing that an elevated expression of the phagocytic receptors Six-Microns-Under (SIMU) and Draper (Drpr) in adult Drosophila glia leads to a loss of both dopaminergic and GABAergic neurons, accompanied by motor dysfunction and a shortened lifespan. Importantly, this reduction in neuronal number is not linked to neuronal apoptosis, but rather to phosphatidylserine-mediated phagoptosis of live neurons by hyper-phagocytic glia. Altogether, our study reveals that the level of glial phagocytic receptors must be tightly regulated for proper brain function and that neurodegeneration occurs not only by defective, but also excessive glial cell function. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu