Autophagy is increased in laminin α2 chain-deficient muscle and its inhibition improves muscle morphology in a mouse model of MDC1A.

@article{Carmignac2011AutophagyII,
  title={Autophagy is increased in laminin $\alpha$2 chain-deficient muscle and its inhibition improves muscle morphology in a mouse model of MDC1A.},
  author={Virginie Carmignac and Martina Svensson and Zandra K{\"o}rner and Linda Elowsson and C{\'i}ntia Yuri Matsumura and Kinga Izabela Gawlik and Val{\'e}rie Allamand and Madeleine Durbeej},
  journal={Human molecular genetics},
  year={2011},
  volume={20 24},
  pages={
          4891-902
        }
}
Congenital muscular dystrophy caused by laminin α2 chain deficiency (also known as MDC1A) is a severe and incapacitating disease, characterized by massive muscle wasting. The ubiquitin-proteasome system plays a major role in muscle wasting and we recently demonstrated that increased proteasomal activity is a feature of MDC1A. The autophagy-lysosome pathway is the other major system involved in degradation of proteins and organelles within the muscle cell. However, it remains to be determined if… 
View on PubMed
academic.oup.com
105 Citations
Highly Influential Citations
4
Background Citations
34
Methods Citations
5
Results Citations
2

Figures from this paper

105 Citations

Citation Type

Citation Type

Publis maintain muscle homeostasis in mouse soleus muscle
TLDR
It is suggested that perlecan inhibits the autophagic process through the activation of the mTORC1 pathway and may be a novel target for enhancing the efficacy of skeletal muscle atrophy treatment.
Aberrant Caspase Activation in Laminin-α2-Deficient Human Myogenic Cells is Mediated by p53 and Sirtuin Activity
TLDR
Aberrant caspase activation in MDC1A cells was mediated both by sirtuin deacetylase activity and by p53, and interventions that inhibit aberrant cospase activation by targeting sIRTuin or p53 function could potentially be useful in ameliorating M DC1A.
Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle.
Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.
Laminin-α2 Chain-Deficient Congenital Muscular Dystrophy: Pathophysiology and Development of Treatment.
  • M. Durbeej
  • Biology, Medicine
    Current topics in membranes
  • 2015
Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy.
Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains
TLDR
It is shown that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models, and a previously unidentified mechanism by which ubiquitin ligases activate autophagic regulators is uncovered.
Investigating Lysosomes and Protein Degradation Pathways for the Treatment of Congenital Muscular Dystrophy Type 1A
TLDR
It is shown that manipulating the membrane-repair and membranefusion capacity of lysosomes with chemicals does not appear to have therapeutic potential, and it is found that MG132, a proteasome inhibitor, partially ameliorates disease pathology in caf mutants.
mTOR dysfunction contributes to vacuolar pathology and weakness in valosin-containing protein associated inclusion body myopathy.
TLDR
It is suggested that VCP mutations may disrupt mTOR signaling and contribute to IBMPFD/ALS disease pathogenesis.
Misregulation of autophagy and protein degradation systems in myopathies and muscular dystrophies
TLDR
The current view on the role of autophagy lysosome and ubiquitin-proteasome in the pathogenesis of myopathies and muscular dystrophies is discussed, and how alteration of these degradative systems contribute to muscle wasting in inherited muscle disorders is discussed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 57 REFERENCES
Proteasome inhibition improves the muscle of laminin α2 chain-deficient mice.
TLDR
It is shown that members of the UPS are upregulated and that the global ubiquitination of proteins is raised in dystrophic limb muscles and that phosphorylation of Akt is diminished in diseased muscles and proteasome inhibition significantly improves the dy(3K)/dy( 3K) phenotype.
Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration
TLDR
Force activation of autophagy by genetic, dietary and pharmacological approaches restored myofiber survival and ameliorated the dystrophic phenotype of Col6a1−/− mice, indicating that defective activation of the autophagic machinery is pathogenic in some congenital muscular dystrophies.
Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not in dystrophin-deficient, mice.
TLDR
BCL2-mediated apoptosis appears to play a significant role in pathogenesis of laminin alpha2 deficiency, but not of dystrophin deficiency, suggesting that therapies designed to ameliorate disease by inhibition of apoptosis are more likely to succeed in MDC1A than in DMD.
Omigapil Ameliorates the Pathology of Muscle Dystrophy Caused by Laminin-α2 Deficiency
TLDR
Treatment with omigapil inhibits apoptosis in muscle, reduces body weight loss and skeletal deformation, increases locomotive activity, and protects from early mortality in the MDC1A mouse model.
Inhibition of apoptosis improves outcome in a model of congenital muscular dystrophy.
TLDR
Bcl-2 family-mediated apoptosis contributes significantly to pathogenesis in the mouse model of CMD1A, and antiapoptosis therapy may be a possible route to amelioration of neuromuscular dysfunction due to laminin-alpha2 deficiency in humans.
Autophagy is required to maintain muscle mass.
Overexpression of mini‐agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin‐α2‐deficient mice
TLDR
The results show that the direct linkage of muscle basal lamina with the sarcolemma is the basis of mini‐agrin‐mediated amelioration and provide unprecedented evidence that this linkage is important for proper regeneration of muscle fibers after injury.
Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies
TLDR
Mice with laminin α2 chain deficiency have analogous phenotypes, and are reliable models for studies of disease mechanisms and potential therapeutic approaches and advances toward the development of treatment are discussed.
Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages
Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown…
Distinct Roles for Laminin Globular Domains in Laminin α1 Chain Mediated Rescue of Murine Laminin α2 Chain Deficiency
TLDR
Overexpression of laminin α1 chain that lacks the dystroglycan binding LG4-5 domains in α2 chain deficient mice resulted in prolonged lifespan and improved health, and showed that lamin in α1LG domains and consequently their receptors have disparate functions in the neuromuscular system.
...
1
2
3
4
5
...