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Caractérisation des anticorps anti-CASPR2 de patients atteints d’encéphalite limbique auto-immune et impact sur le complexe CASPR2/TAG-1/Kv1.2

Abstract : Anti-CASPR2 autoimmune limbic encephalitis is a central nervous system disorder characterized by memory disorders and epilepsy. CASPR2 (Contactin-associated protein-like 2) with its partner TAG-1, is known for its role in the clusterisation of voltage-dependent potassium channels (Kv1.1 and Kv1.2) in the juxtaparanodal region of node of Ranvier; which are essential for the rapid conduction of nerve signals. In addition, an increasing number of studies suggest a role of CASPR2 in synaptic plasticity and neuronal excitability, in relation with the symptoms observed in patients with anti-CASPR2 antibodies. However, the pathogenic role of anti-CASPR2 antibodies in limbic encephalitis remains far from clear. During my thesis I wished to improve our understanding of the mechanisms mediated by anti-CASPR2 antibodies in limbic encephalitis. To this end, I determined the biological characteristics of anti-CASPR2 antibodies, suggesting a direct role of antibodies on CASPR2 function by targeting its N-terminal domains. Furthermore, I identified two potential mechanisms of anti-CASPR2 antibodies on CASPR2/TAG-1 interaction and on Kv1.2 cell surface expression. These works further implicate anti-CASPR2 antibodies in the pathogenicity of autoimmune limbic encephalitis
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Margaux Saint-Martin. Caractérisation des anticorps anti-CASPR2 de patients atteints d’encéphalite limbique auto-immune et impact sur le complexe CASPR2/TAG-1/Kv1.2. Neurosciences. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSE1342⟩. ⟨tel-02071483⟩

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