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.

Targeting Nfix to fix muscular dystrophies / G. Rossi, V. Taglietti, G. Messina. - In: CELL STRESS. - ISSN 2523-0204. - 2:1(2018 Jan), pp. 17-19. [10.15698/cst2018.01.121]

Targeting Nfix to fix muscular dystrophies

G. Rossi
Primo
;
V. Taglietti
Secondo
;
G. Messina
Ultimo
Funding Acquisition
2018

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.
Nfix; muscular dystrophies; satellite cells; skeletal muscle; slow oxidative fibers; slow regeneration
Settore BIO/17 - Istologia
12-dic-2017
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/653016
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