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Rôle des récepteurs P2X4 dans la dégradation d’ApoE : implication dans la maladie d’Alzheimer

Abstract : P2X4 receptors (P2X4R) are purinergic ion channels expressed on neurons and microglia inthe central nervous system. They have been widely studied and have been implicated in manyphysiological and pathological processes. Previous studies conducted in the laboratoryrevealed an interaction between P2X4R and the Apolipoprotein E (ApoE), as well as anincrease in ApoE level in primary macrophages and microglia obtained from mice lackingP2X4R. Based on these results, this thesis aimed to decipher the mechanisms underlyingP2X4R regulation of ApoE levels. In addition, ApoE being a major risk factor forAlzheimer’s disease, part of this work investigated potential implications of P2X4R in thispathology.Results show that P2X4R modulates cathepsin B activity, which in turn promotes ApoElysosomal degradation. APP/PS1 mice lacking P2X4R show an increase in cognitiveperformances, a decrease in soluble Aβ peptide and an increase of microglia ApoE level.These results support that P2X4R modulates ApoE degradation in a cathepsin B-dependantmanner and that its invalidation leads to an improvement in Alzheimer’s pathology.
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Jennifer Hua. Rôle des récepteurs P2X4 dans la dégradation d’ApoE : implication dans la maladie d’Alzheimer. Neurosciences [q-bio.NC]. Université Montpellier, 2019. Français. ⟨NNT : 2019MONTT021⟩. ⟨tel-02464816⟩

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