Muscle first in neurodegenerative disease?

Researchers hunting for the molecular malfunction behind the paralyzing disease spinal muscular atrophy (SMA) might have been looking on the wrong side of the neuromuscular junction, as Rajendra et al. show on page 831. The work suggests that reduced levels of SMA's signature protein, SMN, disrupt the junction from the muscle side.

SMA is the second most prevalent fatal recessive illness after cystic fibrosis. Although its severity varies, the disease often kills patients before age two as motoneurons deteriorate and muscles wither. How reduced amounts of SMN trigger symptoms isn't clear. Because the disease involves neural breakdown, researchers have assumed that the loss of SMN mainly hits motoneurons, not muscles.

To model the disease, Rajendra et al. identified fruit flies that produce too little of the protein. Feeble flight muscles grounded the mutants....