Exercise can stop accumulation of a harmful protein in the brain

Date:

December 23, 2017

Source:

University of Colorado Anschutz Medical Campus

Summary:

While
vigorous exercise on a treadmill has been shown to slow the progression of
Parkinson’s disease in patients, the molecular reasons behind it have remained
a mystery.

While vigorous exercise
on a treadmill has been shown to slow the progression of Parkinson’s disease in
patients, the molecular reasons behind it have remained a mystery.

But now scientists at the
University of Colorado Anschutz Medical Campus may have an answer.

For the first time in a
progressive, age-related mouse model of Parkinson’s, researchers have shown
that exercise on a running wheel can stop the accumulation of the neuronal
protein alpha-synuclein in brain cells.

The work, published Friday
in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate
professor of medicine and Curt Freed, MD, professor of medicine and division
head of the Division of Clinical Pharmacology and Toxicology at the CU School
of Medicine.

The researchers said
clumps of alpha-synuclein are believed to play a central role in the brain cell
death associated with Parkinson’s disease. The mice in the study, like humans,
started to get Parkinson’s symptoms in mid-life. At 12 months of age, running
wheels were put in their cages.

“After three
months,” Zhou said, “the running animals showed much better movement
and cognitive function compared to control transgenic animals which had locked
running wheels.”

Zhou and Freed found that
in the running mice, exercise increased brain and muscle expression of a key
protective gene called DJ-1. Those rare humans born with a mutation in their
DJ-1 gene are guaranteed to get severe Parkinson’s at a relatively young age.

The researchers tested
mice that were missing the DJ-1 gene and discovered that their ability to run
had severely declined, suggesting that the DJ-1 protein is required for normal
movement.

“Our results
indicate that exercise may slow the progression of Parkinson’s disease by
turning on the protective gene DJ-1 and thereby preventing abnormal protein
accumulation in brain,” Freed said.

He explained that his
animal experiments had very real implications for humans.

“Our experiments
show that exercise can get to the heart of the problem in Parkinson’s
disease,” Freed said. “People with Parkinson’s who exercise are
likely able to keep their brain cells from dying.”

Parkinson’s is a disease
caused by the death of brain cells that make a critical chemical called
dopamine. Without dopamine, voluntary movement is impossible. Most people with
Parkinson’s disease take a drug called L-DOPA to treat their symptoms. The oral
drug is converted into dopamine in the brain allowing patients to get up and
move.

In 1988, Freed and his
colleague Robert Breeze, MD, performed the first transplant of human fetal
dopamine cells into a Parkinson’s patient in the United States. His lab is
currently working to convert human embryonic stem cells to dopamine neurons.
These techniques should make it possible to produce unlimited quantities of
dopamine cells for transplant.

Story Source:

Materials provided by University of Colorado Anschutz Medical Campus. Original
written by David Kelly. Note: Content may be edited for style and length.

Journal Reference:

1.    Wenbo Zhou, Jessica
Cummiskey Barkow, Curt R. Freed. Running wheel exercise reduces α-synuclein
aggregation and improves motor and cognitive function in a transgenic mouse
model of Parkinson’s disease. PLOS ONE, 2017; 12 (12): e0190160 DOI:
10.1371/journal.pone.0190160