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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Functional characterization of the beta-amyloid peptide effect on TRPA1 channel

Objectifs

We recently identified an astrocytic calcium channel that is a potential therapeutic target in Alzheimer's disease with a neuroprotective effect. This channel, TRPA1, is activated very early in the pathology and the peptide beta amyloid (Abeta) may interact directly with it. The objective of this project is to characterize how Abeta acts on this astrocytic calcium channel and what is the functional result of this activation.
 

Résumé

The management of Alzheimer's disease encounters a recurring failure of the current therapeutic strategies especially linked to the late detection and intervention. Early intervention, during the prodromal phase, seems essential to offer new hope to patients. It has been shown that hyperactivity of the neurons of the hippocampus is responsible for non-disabling memory deficits that are precursors of the disease. We recently showed that the astrocyte, which is a cell essential for the survival and functioning of neurons, is on the front line in the implementation of this hippocampal neuronal hyperactivity. We have identified an astrocytic molecular actor that could be responsible for this hyperactivity. We now wonder to characterize the mechanisms involved in its activation by Abeta. In parallel, we will characterize the consequences of channel activation on astrocyte function and in particular on the release of gliotransmitters potentially involved in the deleterious neuronal hyperactivity characteristic of the early phases of Alzheimer's disease. This project will allow to understand how the astrocytic TRPA1 channel is involved in the toxicity of the Abeta peptide and thus to strengthen the characterization of a novel therapeutic target and to contribute to propose an innovative and promising therapeutic strategy.
 

Méthodes

electrophysiology, calcium imaging, high resolution imaging, immunohistostainings, animal handling.
 

Références

  • Rush T, Martinez-Hernandez J, Dollmeyer M, Frandemiche ML, Borel E, Boisseau S, Jacquier-Sarlin M, Buisson A. (2018) Synaptotoxicity in Alzheimer's Disease Involved a Dysregulation of Actin Cytoskeleton Dynamics through Cofilin 1 Phosphorylation. J Neurosci. 2018;38(48):10349-10361
  • Bosson A, Paumier A, Boisseau S, Jacquier-Sarlin M, Buisson A, Albrieux M. (2017) TRPA1 channels promote astrocytic Ca2+hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-? peptide. Mol Neurodegener. 12:53.

Domaines d'expertise requis

Alzheimer, glutamate, astrocyte, synapse, calcium signaling

Contacts

M. Albrieux, MCF UGA
Email : mireille.albrieux@univ-grenoble-alpes.fr
Tél : 04 56 52 06 51
 

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Mise à jour le 26 juin 2020

Contacts

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

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