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Dr. Xiangdong William Yang Photo Credit: Courtesy of UCLA/Health |
A new UCLA Health study has discovered in mouse models that genes associated with repairing mismatched DNA are critical in eliciting damages to neurons that are most vulnerable in Huntington's disease and triggering downstream pathologies and motor impairment, shedding light on disease mechanisms and potential new ways to develop therapies.
Huntington’s disease is one of the most common inherited neurodegenerative disorders that typically begins in adulthood and worsens over time. Patients begin to lose neurons in specific regions of the brain responsible for movement control, motor skill learning, language and cognitive function. Patients typically live 15 to 20 years after diagnosis with symptoms worsening over time. There is no known cure or therapy that alters the course of the disease.
The cause of Huntington's disease was discovered over three decades ago--a "genetic stutter" mutation involves repeats of three letters of the DNA, cytosine-adenine-guanine (CAG), in a gene called huntingtin. Healthy individuals usually have 35 or fewer CAG repeats, but people inherited with mutation of 40 or more repeats will develop the disease. The more CAG repeats a person inherits, the earlier the disease onset occurs. However, how the mutation causes the disease remains poorly understood.