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

Marion Szelechowski, Alexandre Bétourné, Yann Monnet, Cécile A. Ferré, Anne Thouard, Charlotte Foret, Jean-Michel Peyrin, Stéphane Hunot and Daniel Gonzalez-Dunia ()
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Marion Szelechowski: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Alexandre Bétourné: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Yann Monnet: ICM
Cécile A. Ferré: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Anne Thouard: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Charlotte Foret: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Jean-Michel Peyrin: CNRS UMR 8256, Biological Adaptation and Ageing
Stéphane Hunot: ICM
Daniel Gonzalez-Dunia: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6181

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