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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Evaluating the efficacy of a new neuroprotective therapeutic target in the early stages of Alzheimer's disease

Objectifs

We recently identified a potential therapeutic target in Alzheimer's disease with a neuroprotective effect. Our objectives are to evaluate the protection of neuronal function induced by the pharmacological inhibition of the identified target and to characterize the short, medium and long-term effects of this neuroprotection on the AD progression at a functional, morphological, biochemical and behavioral level.

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 have a specific pharmacological inhibitor of this actor that we propose to test on transgenic model animals of Alzheimer's disease as soon as the hyperactivity is established. The effects of this treatment will be evaluated longitudinally, during the early and late asymptomatic stages then during the symptomatic phase. We will analyze some morphological, functional and behavioral hallmarks characteristic of the Alzheimer's disease.

Méthodes

Electrophysiology, calcium imaging, behavioral tasks, 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, signaling

Contacts

Mireille Albrieux, MCF
Email : mireille.albrieux@univ-grenoble-alpes.fr
Tél: 0456520651

Mise à jour le 6 juin 2019

Contacts

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

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