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Why Huntington's Shows Up in Midlife

Onset of symptoms may be tied to weakening of neurons, study finds

MONDAY, June 15 (HealthDay News) -- New research from the University of Chicago may help clear up some of the mysteries of Huntington's disease, including why it affects the nervous system only during adulthood.

An inherited and incurable condition, Huntington's disease causes involuntary body movements and problems with mental processing, including dementia. The symptoms usually don't appear until middle age, and the disease is generally fatal 10 to 30 years after onset.

Research at the university's medical school shows that the mutated huntingtin gene, long known to cause the disease, switches on the JNK3 enzyme produced by neurons, the cells that process and carry signals through the nervous system. JNK3 weakens the ability of neurons to carry these messages.

When a person is young, the body's nervous system is strong and vital enough to overcome the enzyme's efforts to slow messaging. But as the person ages, the complex network of nerve trunks, or axons, starts to show wear and becomes more affected by the enzymes, the researchers explained.

"If you take a hit when you're very young, you still are making more and transporting more proteins in each neuron than you need," co-principal investigator Scott Brady, head of anatomy and cell biology at the University of Illinois at Chicago College of Medicine, said in a news release from the university. "But as you get older and older, the neuron produces and transports less. Each hit diminishes the system further. Eventually, the neuron falls below the threshold needed to maintain cell health."

With less and less signaling running through, the neurons begin to die, causing even fewer transmissions to go through and even more cell death, the study authors noted.

Similar gradual loss, the researchers found, occurs in other inherited neurodegenerative diseases that become active only in adults and in Alzheimer's disease.

"There is a common theme and a common Achilles' heel of the neuron that underlies all these diseases," Brady said. "We've invented a word, 'dysferopathy,' (from the Greek 'fero,' to carry or transport) for these adult-onset neurodegenerative diseases. All have disruption of the axonal transport system in common."

The findings appear online in Nature Neuroscience.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more on Huntington's disease.

-- Kevin McKeever

SOURCE: University of Illinois at Chicago, news release, June 14, 2009

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