Enzyme Expression Could Worsen Parkinson's Disease Progression

Increased expression of c-Abl increased α-synuclein clumps in the brain of patients with Parkinson’s disease.

Researchers have found that blocking the enzyme c-Abl can potentially prevent Parkinson’s disease in mice and a chemical tag on the protein α-synuclein could indicate the disease.

"There were indications that c-Abl activity leads to Parkinson's disease, and our experiments show there is indeed a connection," said researcher Ted Dawson, MD, PhD. "There is already a Food and Drug Administration-approved c-Abl inhibiting drug in use for leukemia, so we're interested in whether it could be used safely against Parkinson's disease or as a starting point to develop other treatments."

In a study published by The Journal of Clinical Investigation, researchers engineered mice without the gene for c-Abl, and found that their symptoms were reduced. Mice with increased c-Abl showed worsened symptoms and faster disease progression.

Researchers also found that unmodified mice with an increased production of c-Abl developed the disease. They then examined how c-Abl effects α-synuclein, a protein that clumps in the brain of patients with Parkinson’s disease.

According to the study, c-Abl adds a phosphate group to a specific place on α-synuclein, and they also found that greater expression of c-Abl increased clumping that then worsened symptoms.

"We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson's disease severity," Dr Dawson concluded.