Amyotrophic lateral sclerosis (ALS) is a fatal and non-curable neurodegenerative disease for which the etiology remains poorly understood. However, among the pathophysiological hallmarks observed both in patients and in animal models, mitochondrial dysfunctions appear to be one of the earliest events and thus might be causative for the progressive loss of motor neurons (Le Masson et al, 2014). Therefore, restoring mitochondrial functions could be a therapeutic area of interest in the development of new therapies in the context of ALS.For this purpose, we are interested in the Bornavirus X protein. When it targets the mitochondria, X protein acts on the preservation of mitochondrial function and inhibits neuron apoptosis. X protein has also been shown to protect neurons from degeneration in an animal model of Parkinson's disease (Szelechowski et al, 2014). Moreover, manipulation of the N-terminal sequence of the protein (XA4) enhances both its mitochondrial targeting and its neuroprotective effect.Based on these knowledges, our study aim was to test the neuroprotective potential of both X and XA4 proteins in the SOD1G93A mice model of ALS.Preliminary results obtained demonstrate that both X and XA4 proteins improve motor neuron survival. However, only X protein delays motor impairments while only XA4 protein increases SOD1G93A mice's life expectancy.Together, we hope that this preclinical study will provide new effective therapeutic tools to not only improve the living conditions of ALS patients but also to increase their lifespan.