Brain transportation system defect linked to Huntington's by UCSD team

Researchers at the University of California, San Diego (UCSD) School of Medicine have linked a defective protein in Huntington's disease to gridlock in the transportation system that moves signals and vital protein cargoes within the brain, eventually leading to neuron cell death.

Published in the September 25, 2003 issue of the journal Neuron, their studies in Drosophila, the fruit fly, showed that a protein called huntingtin is critical for normal neuronal transportation. When the protein is defective, however, it appears to physically blocks traffic in the narrow axons that are the long pipes of the nerve cells.

Although defective huntingtin genes have previously been linked to Huntington's disease, this is the first study to illustrate that the defective protein may cause neuronal damage by aggregating (sticking together) and blocking axonal traffic.

"These findings support our hypothesis that blockage of neuronal transportation is related to several neurodegenerative diseases," said the study's senior author, Lawrence S.B. Goldstein, Ph.D., UCSD professor of cellular and molecular medicine and a Howard Hughes Medical Institute investigator. "In a previous studies (Nature, Dec. 6, 2001 and Neuron, Nov. 8, 2001), we provided evidence that a protein linked to plaque accumulation in Alzheimer's disease is involved in brain cellular trafficking."

In the current study, the Goldstein team removed or reduced the normal huntingtin gene in fruit fly larva. As a result, they found that vesicle traffic up and down the axon was disrupted, indicating that huntingtin's normal function was related to the transport machinery.

Next, the researchers looked at the defective, or pathogenic version of the huntingtin protein, and of other proteins that cause polyglutamine diseases, which are neurodegenerative disorders similar to Huntington's disease. They found that the disease-causing versions of all these genes inhibited the transport

Contact: Sue Pondrom
University of California - San Diego

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