Could ozone become a complementary therapeutic approach to improve metabolic and endocrine response of ALS patients?

Abstract Amyotrophic lateral sclerosis (ALS), a devastating progressive neurodegenerative disease, has no effective treatment. Recent evidence supports a strong metabolic component in ALS pathogenesis, raising additional therapeutic targets against ALS. At this respect, improvements in motor deficits and disease-associated weight loss after repeated exposures to ozone (O3) in the mouse model of ALS based on TDP-43 proteinopathy (TDP-43A315T mice) have been reported. Here, the underlying molecular mechanisms to determine whether O3 exposure induces metabolic changes in ALS have been investigated. Molecular biology analysis demonstrated that O3 significantly modified the expression profile of hypothalamic neuropeptides, altering phosphorylation levels of the signal transducer and activator transcription 3 (STAT3) and protein kinase B (Akt), concomitantly to increase the expression of genes involved in metabolism and thermogenesis in the brown adipose tissue (BAT) of TDP-43A315T mice. Composition of fecal gut microbiome of exposed TDP-43A315T mice varied significantly compared to wild type (WT) controls. Densitometric analysis of neuromuscular junction, indicated that O3 does not impaired the progression of disease in the skeletal muscle. Our findings suggest the effectiveness of O3 exposure to induce metabolic effects in the hypothalamus and BAT of this ALS mouse model and may be a new complementary non-pharmacological approach for ALS therapy.