Abstract
Muscle atrophy is an active process controlled by specific transcriptional programs, in which muscle mass is lost by increased protein degradation and/or decreased protein synthesis. This review explores the involvement of Toll-like receptors (TLRs) in the muscle atrophy as it is observed in muscular dystrophies, disorders characterized by successive bouts of muscle fiber degeneration and regeneration in an attempt to repair contraction-induced damage. TLRs are defense receptors that detect infection and recognize self-molecules released from damaged cells. In muscular dystrophies, these receptors become over-active, and are firmly involved in the sustained chronic inflammation exhibited by the muscle tissue, via their induction of pro-inflammatory cytokine expression. Taming the exaggerated activation of TLR2/4 and TLR7/8/9, and their downstream effectors in particular, comes forward as a therapeutic strategy with potential to slow down disease progression.
Highlights
Muscle atrophy is an active process controlled by specific transcriptional programs, in which muscle mass is lost by increased protein degradation and/or decreased protein synthesis
This review explores the involvement of Toll-like receptors (TLRs) in the muscle atrophy as it is observed in muscular dystrophies, disorders characterized by successive bouts of muscle fiber degeneration and regeneration in an attempt to repair contraction-induced damage
Lack of TLR4 function in mice does not alter gastrocnemius muscle mass and cross-sectional area (CSA) [55], while absence of the receptor protected against heat shock protein 70 (HSP70) and HSP90 induced muscle wasting [56]
Summary
Muscular dystrophies are hereditary disorders caused by defects in a plethora of genes involved in muscle protein expression and organization. These diseases share clinical features of progressive loss of muscle strength and dystrophic pathological patterns that can be discerned in the skeletal muscle tissue [1]. The limb girdle muscular dystrophies (LGMDs), a heterogeneous group of diseases caused by different gene defects, represent the second most common dystrophy, and associate with predominant shoulder girdle and pelvic muscle weakness. Myofibers become active participants in the regulation and recruitment of inflammatory cells, by inducing the major histocompatibility complex I (MHC-I) on their sarcolemma and by producing regulatory cytokines, steering the inflammation forward. Glucocorticoids mitigate symptoms and add years to patient mobility, but come with important side effects and do not represent a true cure for the disease
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