Northwestern scientists shed new light on neurodegenerativ...( genome or complete genetic sequence ...)

The researchers injected one group of healthy worms with cells with 19 glutamine residues and another group with cells with 82 glutamine residues. The glutamine residues were attached to a fluorescent reporter, allowing the researchers to view the glutamine residues, protein misfolding and any aggregation in the body wall muscle cells of the worms.

The worms with the soluble protein containing 19 glutamine residues exhibited healthy behavior, moving with normal speed and growing from embryo to adulthood in the expected time of 48 hours. On the other hand, the worms with 82 residues were extremely sluggish, and their growth was slowed. It took them more than twice as long to reach adulthood. Under a microscope, the researchers could see that the fluorescent green glutamine residues were distributed evenly throughout the muscle in the healthy worms, but the residues clearly were aggregated and lumped together in the unhealthy worms. The chronically stressed cells of the unhealthy worms activated the heat shock response.

Morimoto and his team wanted to see if the presence of molecular chaperones had any impact on the aggregates. The researchers co-expressed different yeast heat shock proteins in the worms with the 82 residues. They found that heat shock protein 104 reduced the appearance of polyglutamine aggregates and the associated developmental delay. Other molecular heat shock proteins had no effect. This key finding could aid the development of therapeutic strategies to combat the negative effects of the polyglutamine expansions.

"This is where the race between the body's heat shock proteins and protein misfolding comes in," said Morimoto. "Environmental and physiological stress intensifies misfolding events throughout the body and can divert the molecular chaperones away from the aggregates, accelerating the onset of disease."

The researchers next asked whether or not the soluble and h
'"/>

Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
21-May-2000