Protein Found In Brain Cells May Shed New Light On The Cause Of Dystonia

"Our research shows that the two proteins are almost identical, which implies that they have a similar function. The next step will be to identify the exact role of the torsinB protein," said Stefan-M. Pulst, M.D., who holds the Carmen and Louis Warschaw Chair in Neurology at Cedars-Sinai Medical Center.

Unlike some forms of dystonia, which affect only one part or area of the body, early-onset dystonia is the most severe form of the disease and occurs in childhood. The disorder usually starts with the leg or the foot and eventually affects the child’s entire body. In some families, early-onset dystonia is inherited and has been linked to a gene called DYT1, which makes the torsinA protein. When DYT1 is defective, current scientific thinking is that torsinA fails to function normally, leading to the development of early-onset dystonia. Moreover, the disorder has been linked to a part of the brain called the basal ganglia, which is known to regulate both voluntary and involuntary muscle control.

"Although we don’t know the exact role of the torsin proteins, we do know that the defective form of torsinA somehow disrupts communication among the neurons that regulate muscle control and leads to the symptoms of dystonia," explained Dr. Pulst.

To understand how the torsin proteins might be involved in the development of dystonia, the investigators examined tissue from the adult mouse brain and developing mouse embryo (at different stages of development) to determine where the proteins were expressed. Using specialized laboratory tests, the tissues were stained with antibodies directed to the respective torsin proteins so that the investigators were able to see where torsinA and B were located. With only slight differences, they found that both torsinA and torsinB were widely expressed throughout the adult mouse brain including such structures as the cortex, thalamus, basal ganglia, hippocampus, and cerebellum.

"Because the anatomical distribution of the two proteins were almost identical and not limited to the basal ganglia, other parts of the brain may very well be implicated in the development of early-onset dystonia," said Dr. Pulst.

Additionally, in the developing embryo and mouse brain tissue, the investigators found that torsinA and torsinB were largely expressed in neuronal processes, indicating that the proteins may be involved in regulating the release of neurotransmitters, or the nerve impulses that direct communication between the brain and body.

Although torsinA is abundantly expressed in human tissues that include brain, muscle, liver and kidney, the investigators found no torsin proteins present in the liver, kidney or lungs during embryonic development of the mouse. However, torsin proteins were observed in the heart, cartilage and bone structures.

"The presence of these proteins in cartilage and heart during development, may indicate that the torsin proteins may have important functions outside the brain," said Dr. Pulst.

This research was supported by the F.R.I.E.N.D.S of Neurology and the National Institutes of Health.

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