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Study using robotic microscope shows how mutant Huntington's protein affects neurons

Using a specially designed robotic microscope to study cultured cells, researchers have found evidence that abnormal protein clumps called inclusion bodies in neurons from people with Huntington's disease (HD) prevent cell death. The finding helps to resolve a longstanding debate about the role of these inclusion bodies in HD and other disorders and may help investigators find effective treatments for these diseases. The study was funded primarily by the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and appears in the October 14, 2004, issue of Nature.*

Inclusion bodies are common to many neurodegenerative disorders, including HD, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). The role of inclusion bodies in these diseases has long been controversial. Some studies suggest that they may be a critical part of the disease process, while others indicate that they may help protect the cells from toxic proteins or that they are merely bystanders in the disease process.

One problem in identifying how inclusion bodies influence disease is that researchers have been unable to track changes in individual neurons over time. "It was like viewing pictures of a football game and trying to imagine the score," says Steven Finkbeiner, M.D., Ph.D., of the Gladstone Institute of Neurological Disease and the University of California, San Francisco. "Much was happening that we couldn't see."

To overcome this problem, Dr. Finkbeiner and his colleagues wrote a computer program that allows a microscope to match images in a culture dish to images it has stored and to manipulate its controls to look at the same neurons over and over again - like time-lapse photography. This allowed the investigators to follow changes in a single neuron or a group of neurons over a period of days. They used this automated microscope to study neurons that contained a version of the huntingtin protein that cau
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Contact: Natalie Frazin or Stephanie Clipper
301-496-5924
NIH/National Institute of Neurological Disorders and Stroke
13-Oct-2004


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