Proteins in Eye and Limb Muscles Shed Light on ALS Development

Nerve axons and muscle fibers lose contact early in amyotrophic lateral sclerosis.

A study comparing eye and limb muscles to determine how amyotrophic lateral sclerosis (ALS) develops from a muscular perspective revealed that nerve axons and muscle fibers lose contact early on.

ALS is primarily considered a motor neuron disease, but the study suggests that the loss of contact occurs well before motor neurons begin dying off.

“While skeletal muscles are severely affected in ALS, eye muscles are far less affected than limb muscles,” said researcher Vahid M. Harandi. “In our research, we have been looking at why."

During the study, researchers focused on the expression among the distribution of key neurotrophic factors and Wnt proteins in the limb and eye muscles, which both have been implicated in numerous neuromuscular and neurological disease.

“What we found were intrinsic differences between limb and eye muscles regarding expression of certain signal proteins involved in the development and vitality of neurons,” Harandi said. “These differences, together with the fact that the neuromuscular junctions of eye muscles seem better able to preserve these signal proteins, known as neurotrophic factors, might play a role in the preservation of eye muscle function during ALS.”

The findings suggest that muscle fibers may be responsible for initiating the degeneration of motor neurons in ALS patients.

“ALS has traditionally been considered as primarily a motor neuron disease,” Harandi said. “However, accumulating data indicates that loss of contact between the nerve axons and the muscle fibers occurs early, long before the death of motor neurons. This means that muscle fibers may be what's initiating the motor neuron degeneration. These findings have led to a changing focus in ALS research from motor neurons alone to also include the muscle fibers and the neuromuscular junctions.”