Targeting Nfix to fix muscular dystrophies
Authors:Giuliana Rossi1, Valentina Taglietti2 and Graziella Messina2
1 Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
2 Department of Biosciences, University of Milan, via Celoria 26, 20133, Milan, Italy.
Keywords:
Nfix, skeletal muscle, satellite cells, muscular dystrophies, slow regeneration, slow oxidative fibers.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that they have no conflict of interest.
Please cite this article as:
Giuliana Rossi, Valentina Taglietti and Graziella Messina (2017). Targeting Nfix to fix muscular dystrophies. Cell Stress 2(1): 17-19. doi: 10.15698/cst2018.01.121
© 2017 Rossi et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Muscular dystrophies (MDs) are still incurable heterogeneous diseases, characterized by muscle wasting, replacement by fibrotic tissue, and increasing weakness, which in severe cases, such as Duchenne MD, lead to premature death. MDs are due to mutations encompassing different dystrophin-glycoprotein complex (DGC) genes, which code for structural proteins that anchor the cytoskeleton to the extracellular matrix, thus conferring myofiber stability. All mutations destabilizing this complex result in different MD forms, with varying levels of severity. Independently of the genetic defect, MDs share common hallmarks, characterized by continuous cycles of muscle degeneration, due to lack of structural support during contraction, followed by regeneration cycles by satellite cells (SCs), the canonical myogenic stem cells of adult muscle. However, dystrophic SCs generate new fibres which are also prone to degeneration so that, after many cycles of degeneration/regeneration, this cell population is exhausted and muscle is replaced by connective and adipose tissue. At this stage, any therapeutic intervention is likely to fail.