{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:22:46Z","timestamp":1790788966211,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Association for research on ALS (ARSLA)","award":["20219"],"award-info":[{"award-number":["20219"]}]},{"name":"AFM-T\u00e9l\u00e9thon (Association Fran\u00e7aise pour la Myopathie)","award":["20219"],"award-info":[{"award-number":["20219"]}]},{"name":"Rotary Club of Bergerac, France","award":["20219"],"award-info":[{"award-number":["20219"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model. We first tested in vitro the effect of the X-derived peptide (PX3) on motoneurons primary cultures of SOD1G93A mice. The total intracellular adenosine triphosphate (ATP) content was measured after incubation of the peptide. We next tested in vivo the intramuscular injection of X protein using a canine viral vector (CAV2-X) and PX3 intranasal administrations in SOD1G93A mice. Disease onset and progression were assessed through rotarod performance, functional motor unit analysis via electrophysiology, and motor neuron survival by immunohistochemistry. The results showed that in vitro PX3 restored the ATP level in SOD1G93A motor neurons. In vivo, treated mice demonstrated better motor performance, preserved motor units, and higher motor neuron survival. Although life expectancy was not extended in this severe mouse model of motor neuron degeneration, the present findings clearly demonstrate the neuroprotective potential of X protein in a model of ALS. We are convinced that further studies may improve the therapeutic impact of X protein with optimized administration methods.<\/jats:p>","DOI":"10.3390\/ijms252312789","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T05:19:39Z","timestamp":1732771179000},"page":"12789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4597-7225","authenticated-orcid":false,"given":"Jeflie","family":"Tournezy","sequence":"first","affiliation":[{"name":"Neurocentre Magendie INSERM U1215, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"L\u00e9ger","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie INSERM U1215, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Klonjkowski","sequence":"additional","affiliation":[{"name":"UMR 1161 Virologie, INRA, ANSES, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-7120","authenticated-orcid":false,"given":"Daniel","family":"Gonzalez-Dunia","sequence":"additional","affiliation":[{"name":"Infinity (Toulouse Institute for Infectious and Inflammatory Diseases), INSERM, CNRS, Universit\u00e9 de Toulouse, UPS, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-7413","authenticated-orcid":false,"given":"Marion","family":"Szelechowski","sequence":"additional","affiliation":[{"name":"Infinity (Toulouse Institute for Infectious and Inflammatory Diseases), INSERM, CNRS, Universit\u00e9 de Toulouse, UPS, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Garenne","sequence":"additional","affiliation":[{"name":"IMS Laboratory, UMR5218, CNRS, Bordeaux University, 33400 Talence, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Mathis","sequence":"additional","affiliation":[{"name":"Nerve-Muscle Unit, ALS Center, Department of Neurology, University Hospital (CHU) of Bordeaux (Pellegrin Hospital), 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3552-9137","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Chevallier","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie INSERM U1215, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendal","family":"Le Masson","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie INSERM U1215, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"},{"name":"Nerve-Muscle Unit, ALS Center, Department of Neurology, University Hospital (CHU) of Bordeaux (Pellegrin Hospital), 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41582-018-0103-y","article-title":"Amyotrophic lateral sclerosis\u2014A multisystem neurodegenerative disorder","volume":"15","author":"Grossman","year":"2019","journal-title":"Nat. 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