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Mechanism for neurodenegerative diseases linked to transport proteins

Hampering the transport of proteins within cells may underlie several adult-onset neurodegenerative diseases, such as Huntington's, ALS and Kennedy disease. Understanding how this cell transport is blocked in these diseases may offer targets for future therapy.

In a new study published online June 4 in Nature Neuroscience, researchers from the University of Illinois at Chicago College of Medicine showed how a chemical pathway that is obstructed in Kennedy disease interferes with a cellular distribution system called "fast axonal transport" that moves proteins from where they are synthesized to where they are needed in the cell.

This transport system is critical in neurons because these cells can be as much as three feet long, says Dr. Scott Brady, professor and head of anatomy and cell biology at UIC.

"A breakdown in fast axonal transport would selectively kill neurons because neurons are especially dependent on the transport system," Brady said.

Kennedy disease is also known as spinal and bulbar muscular atrophy, or SBMA. Like the better-known ALS and Huntington's, it is a rare but devastating disease, affecting one in 40,000 people, usually between the ages of 30 and 50. Huntington's strikes about four times as many.

Neurodegenerative diseases like SBMA are caused by the lengthening of part of a gene that encodes repetitions of the amino acid glutamine in the protein. Although different genes are affected, all of the polyglutamine-expansion or "polyQ" diseases are characterized by symptoms that begin in middle age and by the loss of certain types of neurons through a pattern in which the neuron's terminals die before the cell body. PolyQ genes are expressed in many types of cells, but only neurons are affected.

Earlier studies had linked specific neurodegenerative diseases to mutations in proteins involved in intracellular transport. This led researchers to wonder if the deranged polyQ proteins inhibit fast axonal t
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Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
8-Jun-2006


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