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Article Dans Une Revue Cell Reports Année : 2021

VEGF counteracts amyloid-β-induced synaptic dysfunction

Résumé

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.

Domaines

Neurobiologie
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Dates et versions

hal-03447499 , version 1 (29-11-2021)

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Pauline Bouvet, Naura Chounlamountri, Chantal Watrin, Roger Besançon, David Meyronet, et al.. VEGF counteracts amyloid-β-induced synaptic dysfunction. Cell Reports, 2021, 35 (6), pp.109121. ⟨10.1016/j.celrep.2021.109121⟩. ⟨hal-03447499⟩
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