In amyotrophic lateral sclerosis (ALS), neuroscientists have come to believe that overexcitation of motor neurons contributes to excitotoxicity and degeneration. But according to a February 23 paper in the Journal of Neuroscience, busted neural brakes may be another reason for the disease. First author Qing Chang and senior author Lee Martin of the Johns Hopkins University School of Medicine in Baltimore, Maryland, report that glycine-based inhibition of motor neurons is feeble in cultured neurons from ALS model mice.

“You can have overexcitation…but what about insufficient inhibition?” Martin said. “I think that is an equally important component.” Chang studied mice carrying the G93A mutant of the human superoxide dismutase 1 (SOD1) gene, which is associated with some forms of inherited ALS. The scientists are still looking for the specific spanner in the network. But whatever the cause of the disinhibition, Martin speculated that it could lead to a constant low level of activity—wearing out the motor neurons or poisoning them with their own excitotoxic emissions. The work suggests glycine signaling as a potential therapeutic target, said Mingchen Jiang of Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, who was not involved with the study.