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Article Dans Une Revue Nature Communications Année : 2014

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease

Marion Szelechowski
  • Fonction : Auteur
Alexandre Betourne
Yann Monnet
  • Fonction : Auteur
Cecile A. Ferre
  • Fonction : Auteur
Anne Thouard
  • Fonction : Auteur
Charlotte Foret
  • Fonction : Auteur
Stephane Hunot
Daniel Gonzalez-Dunia

Résumé

Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death. We show that the BDV X protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of Parkinson's disease, even when expressed alone outside of the viral context. We also show that intranasal administration of a cell-permeable peptide derived from the X protein is neuroprotective. We establish that both the X protein and the X-derived peptide act by buffering mitochondrial damage and inducing enhanced mitochondrial filamentation. Our results open the way to novel therapies for neurodegenerative diseases by targeting mitochondrial dynamics and thus preventing the earliest steps of neurodegenerative processes in axons.

Dates et versions

hal-01542865 , version 1 (20-06-2017)

Identifiants

Citer

Marion Szelechowski, Alexandre Betourne, Yann Monnet, Cecile A. Ferre, Anne Thouard, et al.. A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease. Nature Communications, 2014, 5, pp.5181. ⟨10.1038/ncomms6181⟩. ⟨hal-01542865⟩
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