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Worm hormone discovery may aid fight against parasitic disease

placing the missing hormones through replacement therapy can relieve the symptoms of the disease, much as providing the missing ligand to the worms restored their normality.

"The conservation of this pathway is remarkable," said Dr. Mangelsdorf, an investigator in UT Southwestern's Howard Hughes Medical Institute (HHMI). "This line of investigation has been much sought-after in terms of how the DAF-12 protein works and whether it had a hormonal regulator. Mother Nature has used this system from the very simplest nematode worms up to humans, not only employing the same types of proteins to do the job, but also the same types of hormones."

The dauer diapause occurs naturally in C. elegans when the worm senses from its environment that conditions are not favorable for maturing, such as when food is scarce. Dr. Mangelsdorf said cholesterol and other signals derived from the worm's food source are required to launch the series of biochemical events leading to the production of the hormonal ligand and continued development. Without these environmental signals and the ligand to activate DAF-12, the worm's life remains suspended.

The UT Southwestern research also may aid in the fight against human disease because the dauer diapause stage of C. elegans is very similar to the infective state of parasitic nematodes. According to the World Health Organization, such parasites infect about 2 billion people worldwide and severely sicken some 300 million, at least 50 percent of whom are school-age children.

In the infective state, parasitic nematodes, such as hookworms, remain in a larval, "resting" stage until they enter the human body, where they eventually migrate to the intestine and begin to mature. Dr. Mangelsdorf is investigating whether the homologue of DAF-12 in parasitic nematodes may regulate their maturing activity as well. If so, he said, the same pathway could be exploited to eradicate the pests, either by keeping them perpetually in a
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Source:UT Southwestern Medical Center


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