Aim: 

ALS is a neurodegenerative disease characterized by motoneuronal loss, and muscle atrophy. 20% of the familial ALS cases have been linked to Cu/Zn superoxide dismutase 1 (SOD1) mutations. Many evidence suggests that mutated SOD1 toxicity is non-cell autonomous, involving multiple cell types. Degeneration of the neuromuscular junction in SOD1-mutant mice takes place long before motoneuronal death, leading to hypothesize that muscle might be a source of toxicity.

Methods: 

Using cultures of myoblasts and gastrocnemio muscles of SOD1-mice, we evaluated the effect of mutant SOD1 on the expression of proteins involved in muscle physio-pathology: the myogenic regulatory factors (MRFs) MyoD and myogenin, atrogin-1, and TGFb1.

Results: 

Mutant-SOD1 increases the expression of these genes both in vitro and in vivo, and alterations in the expression pattern of these genes occur already at the pre-symptomatic stage, preceding motoneuronal loss. Since recently it has been shown an increased risk for ALS in male soccer players, possibly linked to the abuse of anabolic substances, we evaluated, in SOD1-mutant mice, the effect of the anabolic steroid nandrolone on the expression of the same muscle proteins. Nandrolone administration did not modify the expression of MRFs and atrogin-1, while it further increased TGFb1 expression.

Conclusion: 

Data obtained indicate that ALS skeletal muscles might have an impaired regenerative potential and might be more prone to atrophy. (Grants: Telethonn Ministry of Labour - Health and Social Affairs, Fondazione Cariplo, UNIMI)