VEGF counteracts amyloid-β-induced synaptic dysfunction.

Autor:	Martin L; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Bouvet P; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Chounlamountri N; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Watrin C; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Besançon R; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Pinatel D; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Meyronet D; Université Claude Bernard Lyon 1, 69000 Lyon, France; Cancer Research Center of Lyon, Cancer Cell Plasticity, INSERM U1052, CNRS UMR5286, 69000 Lyon, France; Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon 69000 Lyon, France., Honnorat J; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France., Buisson A; GIN, INSERM U1216, Université Grenoble Alpes, 38000 Grenoble, France., Salin PA; Université Claude Bernard Lyon 1, 69000 Lyon, France; Lyon Neuroscience Research Center, Forgetting processes and cortical dynamics, INSERM U1028, CNRS UMR5292, 69675 Bron, France., Meissirel C; Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France. Electronic address: claire.meissirel@inserm.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 May 11; Vol. 35 (6), pp. 109121.
DOI:	10.1016/j.celrep.2021.109121
Abstrakt:	The vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aβo). Here, we show that VEGF accumulates in and around Aβ plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aβo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Notably, we demonstrate that VEGF gain of function rescues basal synaptic transmission, long-term potentiation (LTP), and dendritic spine alterations, and blocks long-term depression (LTD) facilitation triggered by Aβo. We further decipher underlying mechanisms and find that VEGF inhibits the caspase-3-calcineurin pathway responsible for postsynaptic glutamate receptor loss due to Aβo. These findings provide evidence for alterations of the VEGF pathway in AD models and suggest that restoring VEGF action on neurons may rescue synaptic dysfunction in AD. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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