Protein "plaque" triggers cell death

Cause of hereditary motion disorder discovered

Brain Research Center J lich
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Coordination disorders and speech difficulties are the consequences of an incurable nerve disease, the "spinocerebellar ataxia". Now a Berlin scientist has decrypted a mechanism that influences the course of the disease: Deficiency is protein deposits in the neurons, which form a veritable "plaque" and thereby kill the cells.

They fall ill between the ages of 30 and 40, have a staggering gait, are barely able to coordinate their hand and leg movements and have a vague, washed-out language: These people suffer from a "spinocerebellar ataxia", a genetically caused, incurable neuropathy of which there are over 28 different forms. The symptoms are triggered by dying nerve cells in the cerebellum, the center that controls the unconscious movements of the body.

Decoded cell death

Now Annett Böddrich from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch has found out that the cause of cell death in spinocerebellar ataxia type 3 is certain protein deposits in the neurons. These are formed from a disease-causing (pathogenic) form of the protein Atx-3 and are influenced by the so-called valosin-containing protein VCP.

The researchers were able to identify a protein consisting of four protein building blocks (amino acids) on the protein Atx-3, to which VCP binds. VCP plays a vital role in vital processes in the cell, such as the breakdown of unwanted or inoperative proteins. As you can now see in the test tube as well as in experiments with the fruit fly Drosophila, VCP, if it is present in excess compared to Atx-3, prevents the formation of protein clots. On the other hand, if the cell has too little VCP relative to Atx-3, harmful plaques are formed.

Thus, high VCP concentrations could reduce the formation of Atx-3 plaques in visual cells of the fruit fly and thereby prevent the death of these cells. The molecular mechanism by which VCP reduces the harmfulness of pathogenic Atx-3 is still unclear. This should now clarify further research. display

(Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, 07.04.2006 - AHE)