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Nat Commun. 2014 Oct 21;5:5181. doi: 10.1038/ncomms6181.

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

Author information

1
1] INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, F-31300, France [2] CNRS UMR 5282, Toulouse, F-31300, France [3] Université Toulouse III Paul Sabatier, Toulouse, F-31300, France.
2
1] ICM, Paris, F-75013, France [2] Sorbonne Universités, UPMC Université Paris 06, UM 75, ICM, Paris, F-75005, France [3] CNRS, UMR 7225, ICM, Paris, F-75013, France [4] Inserm, U 1127, ICM, Paris, F-75013, France.
3
1] CNRS UMR 8256, Biological Adaptation and Ageing, Paris, F-75005, France [2] Sorbonne Universités, UPMC Université Paris 06, UMR 8256, B2A, Biological Adaptation and Ageing, Institut de Biologie Paris Seine, Paris, F-75005, France.

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.

PMID:
25333748
DOI:
10.1038/ncomms6181
[Indexed for MEDLINE]

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