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Role of stearoyl-CoA desaturase-1 in maintaining muscle activity : study of a lesion model for understanding the meatbolic alterations characteristics of amyotrophic lateral sclerosis

Abstract : ALS patients and mouse model manifest metabolic dysfunctions that coincide with the modified levels of various lipid species. We postulated that metabolic dysfunctions in muscles function as a leading preliminary change in ALS. We have noted that the expression of stearoyl-CoA desaturase 1 (SCD1), a key enzyme that synthesises monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs), is diminished even at pre-symptomatic stage in the muscles of an ALS mouse model. In these mice, alterations in circulating and hepatic fatty acid composition, resulting from SCD1 modification, arise at a critical stage of disease onset. Of note, inhibition of SCD1 enzymatic activity by a specific pharmacological agent mimics the metabolicphenotype of the ALS mouse model. Our study also elucidates that the lack of SCD1 plays a vital role in neuromuscular function. It modulates energy supply, and maintains muscle activity by increasing oxidative metabolism and the expression of genes involved in neuromuscular junction development and function. In addition, ablation of SCD1 gene stimulates functional recovery of muscles after a nerve lesion. Pharmacological SCD1 inhibition also provides a protection to muscle function. We conclude that alteration in SCD1 expression and related altered fatty acid profile may protect muscles against pathology. Therefore, SCD1 inhibitors can be developed as a therapeutic intervention.
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Submitted on : Friday, December 20, 2013 - 1:47:12 PM
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Ghulam Hussain. Role of stearoyl-CoA desaturase-1 in maintaining muscle activity : study of a lesion model for understanding the meatbolic alterations characteristics of amyotrophic lateral sclerosis. Biochemistry, Molecular Biology. Université de Strasbourg, 2013. English. ⟨NNT : 2013STRAJ022⟩. ⟨tel-00921430⟩

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