Inhibition of Mitochondrial Fission Protein Drp1 Ameliorates Myopathy in the D2-mdx Model of Duchenne Muscular Dystrophy DOI Creative Commons

H. Grace Rosen,

Nicolas Berger,

Shantel N. Hodge

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

ABSTRACT Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need identify novel targets develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance mitochondrial dynamics (fission and fusion) crucial maintain function skeletal muscle health. Excessive activation Dynamin-Related Protein 1 (Drp1)-mediated fission was reported animal models However, whether Drp1-mediated viable target treating myopathy DMD unknown. Here, we treated D2-mdx model (9-10 weeks old) with Mdivi-1, selective Drp1 inhibitor, every other day (i.p. injection) 5 weeks. We demonstrated that Mdivi-1 effectively improved strength reduced serum creatine kinase concentration. treatment also inhibited regulatory protein markers, Drp1(Ser616) phosphorylation Fis1 muscles from mice, which resulted content damaged fragmented mitochondria. Furthermore, attenuated lipid peroxidation product, 4-HNE, inversely correlated grip strength. Finally, revealed downregulated Alpha Type I Collagen (Col1a1) expression, marker fibrosis, Interleukin-6 (IL-6) mRNA inflammation. In summary, these results demonstrate inhibition by improving alleviating damage mice. These improvements are associated integrity, leading peroxidation.

Language: Английский

Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling DOI Creative Commons
Davide Cervia, Silvia Zecchini, Luca Pincigher

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 225, P. 193 - 207

Published: Sept. 24, 2024

Language: Английский

Citations

4
Identification of VDAC1 as a mitochondria-related target of Duchenne muscular dystrophy based on bioinformatics analysis and in vitro experiments DOI

Wenjuan Wu,

Xueqin Song, Baoguang Li

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 158, P. 114836 - 114836

Published: May 12, 2025

Language: Английский

Citations

0
The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy DOI Open Access
Kajetan Kiełbowski,

Estera Bakinowska,

Grzegorz Procyk

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6108 - 6108

Published: June 1, 2024

Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder associated with muscle wasting and degeneration. The disease caused by mutations in the gene that encodes dystrophin, a protein links cytoskeleton cell membrane proteins. current treatment methods aim to relieve symptoms of or partially rescue functionality. However, they are insufficient suppress progression. In recent years, studies have uncovered important role for non-coding RNAs (ncRNAs) regulating progression numerous diseases. ncRNAs, such as micro-RNAs (miRNAs), bind their target messenger (mRNAs) translation. Understanding mechanisms involving dysregulated miRNAs can improve diagnosis suggest novel patients DMD. This review presents available evidence on altered expression pathogenesis We discuss involvement these molecules processes physiology DMD-associated cardiomyopathy.

Language: Английский

Citations

3
Chimeric Cell Therapy Transfers Healthy Donor Mitochondria in Duchenne Muscular Dystrophy DOI Creative Commons
Maria Siemionow, Katarzyna Bocian,

Katarzyna Bożyk

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(7), P. 1819 - 1829

Published: July 17, 2024

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by dystrophin gene mutations and mitochondrial dysfunction, leading to progressive muscle weakness premature death of DMD patients. We developed human Dystrophin Expressing Chimeric (DEC) cells, created the fusion myoblasts from normal donors patients, as foundation for DT-DEC01 therapy DMD. Our preclinical studies on mdx mouse models revealed enhanced expression functional improvements in cardiac, respiratory, skeletal muscles after systemic intraosseous DEC administration. The current study explored feasibility transfer within which crucial developing new therapeutic strategies Following staining with MitoTracker Deep Red Green dyes, was assessed Flow cytometry (FACS) confocal microscopy. PEG-mediated healthy (MB

Language: Английский

Citations

3
Construction and Application of a Static Magnetic Field Exposure Apparatus for Biological Research in Aqueous Model Systems and Cell Culture DOI Creative Commons

Jana Vučković,

Hakki Gurhan, Belén Rivero‐Gutiérrez

et al.

BIO-PROTOCOL, Journal Year: 2024, Volume and Issue: 14(1354)

Published: Jan. 1, 2024

With the growth of quantum biology field, study magnetic field (MF) effects on biological processes and their potential therapeutic applications has attracted much attention. However, most biologists lack experience needed to construct an MF exposure apparatus own, no consensus standard exists for methods, protocols model organisms are sorely lacking. We aim provide those interested in entering with ability investigate static own research. This protocol covers how design, build, calibrate, operate a chamber (MagShield apparatus), instructions modify parameters other specific needs. The MagShield is constructed mu-metal (which blocks external MFs), allowing generation experimentally controlled MFs via 3-axial Helmholtz coils. Precise manipulation strengths across physiologically relevant range possible: nT hypomagnetic fields, μT < 1 mT weak MFs, moderate several mT. An integrated partition enables different control experimental run simultaneously. demonstrate (with example results) use

Language: Английский

Citations

2
Pathological Defects in a Drosophila Model of Alzheimer’s Disease and Beneficial Effects of the Natural Product Lisosan G DOI Creative Commons
Silvia Bongiorni, Elisabetta Catalani, Ivan Arisi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 855 - 855

Published: July 15, 2024

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize onset pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on β (Aβ)-peptide production accumulation and, consequently, AD We exploited fruit fly

Language: Английский

Citations

1
Inhibition of Mitochondrial Fission Protein Drp1 Ameliorates Myopathy in the D2-mdx Model of Duchenne Muscular Dystrophy DOI Creative Commons

H. Grace Rosen,

Nicolas Berger,

Shantel N. Hodge

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

ABSTRACT Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need identify novel targets develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance mitochondrial dynamics (fission and fusion) crucial maintain function skeletal muscle health. Excessive activation Dynamin-Related Protein 1 (Drp1)-mediated fission was reported animal models However, whether Drp1-mediated viable target treating myopathy DMD unknown. Here, we treated D2-mdx model (9-10 weeks old) with Mdivi-1, selective Drp1 inhibitor, every other day (i.p. injection) 5 weeks. We demonstrated that Mdivi-1 effectively improved strength reduced serum creatine kinase concentration. treatment also inhibited regulatory protein markers, Drp1(Ser616) phosphorylation Fis1 muscles from mice, which resulted content damaged fragmented mitochondria. Furthermore, attenuated lipid peroxidation product, 4-HNE, inversely correlated grip strength. Finally, revealed downregulated Alpha Type I Collagen (Col1a1) expression, marker fibrosis, Interleukin-6 (IL-6) mRNA inflammation. In summary, these results demonstrate inhibition by improving alleviating damage mice. These improvements are associated integrity, leading peroxidation.

Language: Английский

Citations

1