Accumulation of abnormal protein inclusions is implicated in motor neuron 
degeneration in amyotrophic lateral sclerosis (ALS). Autophagy, an intracellular 
process targeting misfolded proteins and damaged organelles for lysosomal 
degradation, plays crucial roles in survival and diseased conditions. Efforts 
were made to understand the role of autophagy in motor neuron degeneration and 
to target autophagy in motor neuron for ALS treatment. However, results were 
quite contradictory. Possible autophagy defects in other cell types may also 
complicate the results. Here, we examined autophagy activity in skeletal muscle 
of an ALS mouse model G93A. Through overexpression of a fluorescent protein 
LC3-RFP, we found a basal increase in autophagosome formation in G93A muscle 
during disease progression when the mice were on a regular diet. As expected, an 
autophagy induction procedure (starvation plus colchicine) enhanced autophagy 
flux in skeletal muscle of normal mice. However, in response to the same 
autophagy induction procedure, G93A muscle showed significant reduction in the 
autophagy flux. Immunoblot analysis revealed that increased cleaved caspase-3 
associated with apoptosis was linked to the cleavage of several key proteins 
involved in autophagy, including Beclin-1, which is an essential molecule 
connecting autophagy and apoptosis pathways. Taking together, we provide the 
evidence that the cytoprotective autophagy pathway is suppressed in G93A 
skeletal muscle and this suppression may link to the enhanced apoptosis during 
ALS progression. The abnormal autophagy activity in skeletal muscle likely 
contributes muscle degeneration and disease progression in ALS.