We undertook a longitudinal study of the histological and biochemical changes at 
the neuromuscular junction (NMJ) in muscles of SOD1-G93A mice. We also assessed 
these functions in mice treated with a known heat shock protein inducer, 
arimoclomol. Tissue samples of treated and untreated mSOD mice were analysed for 
AChE and ChAT enzyme activities as markers of neuromuscular function. Sections 
of hindlimb muscles (TA, EDL and soleus) were also stained for succinate 
dehydrogenase and silver cholinesterase activities as well as for 
immunohistochemistry. Hsp70 levels were also measured from muscle samples using 
ELISA. Results showed that denervation and nerve sprouting were present at 
symptom onset in fast muscles, although slow muscles remained fully innervated. 
Cholinergic enzyme activities were reduced prior to denervation and declined 
further with disease progression. Reduction of endplate size, a slow to fast 
shift in muscle phenotype was also observed. Treatment with arimoclomol delayed 
the appearance of these changes, increased innervation, cholinergic enzyme 
activities and endplate size and reversed muscle fibre transformation. These 
beneficial effects of arimoclomol in muscles were accompanied by an increase in 
Hsp70 expression. In conclusion, our results indicate that pharmacological 
targeting of muscles at early stages of disease may be a successful strategy to 
ameliorate disease progression in ALS.