Studies Strengthen Role of Glutamate, Abnormal RNA

by Margaret Wahl on Thu, 2004-04-01 07:00
Jeffrey Rothstein
Jeffrey Rothstein

Two recent studies strengthen the role of glutamate, a chemical that normally transmits signals between cells in the central nervous system, in causing or perpetuating ALS.

The first, which included MDA research grantee Jeffrey Rothstein at Johns Hopkins University Medical Center in Baltimore, where he directs the MDA/ALS Center, casts suspicion on a glutamate transporter, a protein that takes glutamate away from the area between nerve cells after it has transmitted a signal from one cell to another.

The second, a Japanese study, implicates excessive permeability in a glutamate receptor, a docking site on the surface of motor neurons that receives glutamate and transmits its signal to the cell’s interior.

The glutamate transporter study, published online Feb. 18 in Annals of Neurology, found that people with ALS make more of a glutamate transporter variant called EAAT2b and less of one called EAAT2, while people without ALS make mostly EAAT2 and very little EAAT2b.

The presence of EAAT2b instead of EAAT2 is thought to be due to a difference in the processing of RNA, the middle step in the transition from genes (DNA) to proteins (such as glutamate transporters) in cells. This difference may contribute to a toxic buildup of glutamate around nerve cells.

In the second study, Shin Kwak at the University of Tokyo and colleagues writing in the Feb. 26 issue of Nature, also implicate deficient RNA processing.

The Japanese group found that most of the motor neurons from ALS patients whom they studied had a defect in a late step in processing the RNA instructions for their glutamate receptors, while none of the motor neurons from those without ALS had this defect. This processing failure results in a structure that allows calcium into the motor neuron, a potential source of toxicity.

Margaret Wahl
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