Huntington's disease is characterized by the progressive loss of
nerve cells in the brain and affects approximately one in 10,000 people.
This fatal disorder is caused by a hereditary defect in a single gene.
The debilitating symptoms of Huntington's disease typically manifest
in adulthood and involve loss of motor and cognitive function,
depression and personality changes. From the point of onset, symptoms
develop and intensify over the following 10 to 25 years until death,
typically due to complications associated with the disease.
‘Patients with Huntington's disease have fewer nerve cells in the subthalamic nucleus, a group of brain structures critical for movement and impulse control.’
Currently, there is no cure for Huntington's disease; treatment can
only alleviate some of the symptoms.
Northwestern Medicine scientists identified a link between
Huntington's disease and dysfunction of the subthalamic nucleus, a
component of the basal ganglia, a group of brain structures critical for
movement and impulse control.
"Although the genetic basis of the disease is well established, why
the mutation leads to the expression of symptoms and loss of brain
tissue remains poorly understood," explained senior author Mark Bevan,
professor of physiology at Northwestern University Feinberg School of
The study was published in the journal eLife
"While research into Huntington's disease has focused on other parts
of the basal ganglia, the subthalamic nucleus has been largely
overlooked," said Bevan. "This is surprising because patients with
Huntington's disease have fewer nerve cells in the subthalamic nucleus.
People who have suffered damage to the subthalamic nucleus exhibit
excessive movement and impulsive behavior, similar to patients with
Using mice genetically engineered to carry the Huntington's disease
gene, scientists discovered the electrical activity of the subthalamic
nucleus was lost. Furthermore, impaired subthalamic activity was caused
by anomalous receptor signaling, leading to defective energy metabolism
and accumulation of damaging oxidants.
The authors also found
abnormalities in the subthalamic nucleus occur earlier than in other
brain regions, and that subthalamic nucleus nerve cells progressively
degenerate as the mice age, mirroring the human pathology of
"Our findings suggest early problems in the subthalamic nucleus not
only contribute to the symptoms of Huntington's disease, but are also
likely to impair the processing capacity and health of other brain
structures, more traditionally associated with the disease," Bevan said.
A better understanding of aberrant
brain receptor signaling that leads to nerve cell dysfunction could
reveal a target for therapy, according to the authors.