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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Functional characterization of the Abeta peptide impact on astrocytic TRPA1 channel

Objectifs

The objective of this project is to understand how the Abeta peptide activates the TRPA1 channel, whether it interacts with the channel directly or indirectly and how we can modulate or prevent this activation to block deleterious cascade of events leading to pathogenesis.
 

Résumé

We recently uncovered a novel neuroprotective therapeutic target, TRPA1 channel, effective in a mouse model of Alzheimer's disease. This astrocytic channel is activated by the amyloid beta peptide and subsequently leads to neighboring neuronal hyperactivity that progressively triggers irreversible neurodegeneration. The objective of this project is to characterize how the amyloid beta peptide acts on the TRPA1 channel and what are the functional consequences of this activation which will ultimately lead to nearby neuronal hyperactivity. We propose to address this question at a molecular, cellular and functional level. This project will allow to strengthen the characterization of a novel therapeutic target and will contribute to propose an innovative and promising therapeutic strategy.
 

Méthodes

The Xenopus oocyte model allows heterologous expression and functional characterization of TRPA1 via real-time recordings of the electrical currents generated by these channels giving access to structure-function study. Acute mouse brain slices give access to both neuronal (patch-clamp recording) and astrocytic activity (confocal calcium imaging) on a preserved hippocampal network and to decode disrupted astrocyte-neuron interaction.
 

Références

  • Paumier A, Boisseau S, Pernet-Gallay K, Buisson A, Albrieux M. Astrocyte-neuron interplay is critical for Alzheimer’s disease pathogenesis and is rescued by TRPA1 channel blockade. BioRxiv. 2021. 437466.

Domaines d'expertise requis

Neurophysiology, electrophysiology, calcium, astrocyte-neuron interaction, synapse plasticity

Contacts

Mireille Albrieux, MCF, UGA
Email : mireille.albrieux@univ-grenoble-alpes.fr
Phone : 33 (0)4 56 52 06 51
 

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Mise à jour le 24 juin 2021

Contacts

Pour les stages (master, licence, 3ème), envoyer directement un email au responsable de l'équipe que vous avez identifiée.

Pour une candidature spontanée pour un emploi et uniquement pour cela, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.

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