LEDT and Idebenone treatment modulate autophagy and improve regenerative capacity in the dystrophic muscle through an AMPK-pathway.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Muscle, Skeletal*/metabolism ; Muscular Dystrophy, Duchenne*/drug therapy ; Muscular Dystrophy, Duchenne*/metabolism; Ubiquinone/*analogs & derivatives; Animals ; Mice ; Humans ; Mice, Inbred mdx ; AMP-Activated Protein Kinases/metabolism ; Autophagy ; Disease Models, Animal

Purpose: Considering the difficulties and challenges in Duchenne muscular dystrophy (DMD) treatment, such as the adverse effects of glucocorticoids, which are the main medical prescription used by dystrophic patients, new treatment concepts for dystrophic therapy are very necessary. Thus, in this study, we explore the effects of photobiomodulation (PBM; a non-invasive therapy) and Idebenone (IDE) treatment (a potent antioxidant), applied alone or in association, in dystrophic muscle cells and the quadriceps muscle, with special focus on autophagy and regenerative pathways.
Methods: For the in vitro studies, the dystrophic primary muscle cells received 0.5J LEDT and 0.06μM IDE; and for the in vivo studies, the dystrophic quadriceps muscle received 3J LEDT and the mdx mice were treated with 200mg/kg IDE.
Results: LEDT and IDE treatment modulate autophagy by increasing autophagy markers (SQSTM1/p62, Beclin and Parkin) and signaling pathways (AMPK and TGF-β). Concomitantly, the treatments prevented muscle degeneration by reducing the number of IgG-positive fibers and the fibers with a central nucleus; decreasing the fibrotic area; up-regulating the myogenin and MCH-slow levels; and down-regulating the MyoD and MHC-fast levels.
Conclusion: These results suggest that LEDT and IDE treatments enhance autophagy and prevented muscle degeneration in the dystrophic muscle of the experimental model. These findings illustrate the potential efficacy of LEDT and IDE treatment as an alternative therapy focused on muscle recovery in the dystrophic patient.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright: © 2024 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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EC 2.7.11.31 (AMP-Activated Protein Kinases)
HB6PN45W4J (idebenone)
1339-63-5 (Ubiquinone)

Date Created: 20240318 Date Completed: 20240320 Latest Revision: 20240321

20240321

PMC10947673

10.1371/journal.pone.0300006

38498472