Enzyme fights mutated protein in inherited Parkinson's disease

Jun 26, 2009
Dr. Matthew Goldberg, assistant professor of neurology and psychiatry and senior author of the paper (right); with Xiaodong Ding, senior research associate work at UT Southwestern Medical Center. Credit: UT Southwestern Medical Center

An enzyme that naturally occurs in the brain helps destroy the mutated protein that is the most common cause of inherited Parkinson's disease, researchers at UT Southwestern Medical Center have found.

Their study, using human cells, provides a focus for further research into halting the action of the mutated protein. One of the most famous carriers of the mutation is Google co-founder , who wrote about it on his blog in 2008.

"There are currently enormous efforts to identify potential therapies based on inhibiting this mutated protein," said Dr. Matthew Goldberg, assistant professor of neurology and psychiatry and senior author of the paper, which appears online in the journal Public Library of Science.

"Our paper is a major advance because we identify a protein that binds to the mutated protein and promotes its breakdown," he said.

The particular mutation that they studied affects a protein whose function is not well understood. In its normal form, it appears to have multiple sites where other can attach themselves, like a space station with many docking areas.

Several mutations can affect the protein, which is named LRRK2. Some of the mutations cause .

The current theory is that the mutation leads to increased function of LRRK2 and to the formation of abnormal clumps of proteins inside brain nerve cells. The cells eventually die from these effects.

In the current study, the researchers used cultured human kidney cells and found that LRRK2 and a protein called CHIP "robustly" associated with each other.

Further testing showed that CHIP and LRRK2 could bind to each other in two different ways, either directly or indirectly by a third molecule that acted as a bridge.

When CHIP bound to either the normal or mutant form of LRRK2, levels of LRRK2 in the cell decreased, the researchers found. This occurred because the cells increased the rate at which they destroyed LRRK2.

"CHIP may be a useful therapeutic target for treatments to break down LRRK2 in people with Parkinson's," Dr. Goldberg said.

"Our next step is to identify cellular mechanisms that signal LRRK2 to be degraded by CHIP or by other mechanisms," he said. "Because LRRK2 mutations are believed to cause Parkinsonism by increasing the activity of LRRK2, enhancing the normal mechanisms that target LRRK2 for degradation by CHIP may be therapeutically beneficial."

Source: UT Southwestern Medical Center (news : web)

Explore further: Education, breastfeeding and gender affect the microbes on our bodies

add to favorites email to friend print save as pdf

Related Stories

Parkinson's mutation stunts neurons

Nov 22, 2006

Mutations in a key brain protein known to underlie a form of Parkinson's disease wreaks its damage by stunting the normal growth and branching of neurons, researchers have found. They have pinpointed the malfunction of the ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

6 hours ago

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

17 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

18 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

User comments : 0

More news stories

Vietnam battles fatal measles outbreak

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

Under some LED bulbs whites aren't 'whiter than white'

For years, companies have been adding whiteners to laundry detergent, paints, plastics, paper and fabrics to make whites look "whiter than white," but now, with a switch away from incandescent and fluorescent lighting, different ...