title: A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease.
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.
authors.affiliation: 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.
authors.forename: Marion
authors.initials: M
authors.lastname: Szelechowski
authors.affiliation: 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.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bétourné
authors.affiliation: 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.
authors.forename: Yann
authors.initials: Y
authors.lastname: Monnet
authors.affiliation: 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.
authors.forename: Cécile A
authors.initials: CA
authors.lastname: Ferré
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Thouard
authors.affiliation: 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.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Foret
authors.affiliation: 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.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Peyrin
authors.affiliation: 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.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hunot
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez-Dunia
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000517:prevention & control* / Q000821:virology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000517:prevention & control* / Q000821:virology; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000737:chemistry*
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D017361:Viral Nonstructural Proteins; D012402:Rotenone