An inherited enzyme defect identified in 1993 accounts for only a few percent of the cases. Now, researchers have evidence suggesting that many ALS cases, perhaps the majority, result from abnormal genetic instructions that leave the brain and spinal cord unable to sponge up glutamate, a potentially destructive amino acid.
Neurons normally release small amounts of glutamate to signal neighboring cells.
Yet because exposure to large quantities of this neurotransmitter can kill neurons, cell surface proteins known as glutamate transporters must quickly recycle the amino acid. At last week's Society for Neuroscience meeting in Washington, D.C., Jeffrey D. Rothstein of Johns Hopkins University in Baltimore and his colleagues described a study of one glutamate transporter, EAAT2. When the researchers examined tissues from 20 people who had died of ALS, they found that 10 had frequently harbored mutations in the genetic instructions used to construct that crucial transporter. The protein-making equipment of cells reads these strands of mRNA to determine which amino acids to link together. In their study of brain and spinal cord tissue from people who had died of ALS, Rothstein's group examined the mRNAs created from the gene for EAAT2.