Under the Hood

Parkinson’s Gene Kills Off Brain Cells It’s Supposed To Protect

A gene linked to Parkinson’s disease is doing the opposite of what it’s supposed to for the people with that neurodegenerative illness, new research suggests.

The U.S. National Institute of Neurological Disorders and Stroke funded a study that focuses on the LRRK2 gene, what the group calls “the most common genetic cause for late-onset Parkinson’s disease.” Although scientists have known that mutations of the gene were linked to the disease, which degrades a person’s motor function, it has been unclear exactly how the gene plays a role in Parkinson’s and what it is meant to do in a healthy brain. But new research shows that LRRK2 is actually meant to protect the very brain cells that are targeted most by Parkinson’s.

The disease is most well-known for the subtle hand tremors that occur in its beginning stages. As the illness progresses, patients lose control over automatic functions like blinking; have slurred speech; get stiff muscles; and could have balance issues, among other symptoms.

LRRK2 mutations are one thing associated with the onset of Parkinson’s, bringing on the disease’s symptoms as people get older.

“Parkinson’s-linked mutations such as LRRK2 have subtle effects that do not produce symptoms until late in life,” senior study author Jie Shen said in the NINDS statement. “Understanding the normal function of these types of genes will help us figure out what has gone wrong to cause disease.”

While studying LRRK2, researchers used mice. In those animals, this gene doesn’t have a heavy effect, perhaps because they also have an LRRK1 gene that can step in during their short lives to make up for mutations of the other gene in the pair. To imitate a human brain, the scientists removed both the LRRK1 and LRRK2 genes from the mouse brains and observed what happened — the mice lost neurons that contain dopamine in the parts of the brain that are classically affected during the disease’s progression in humans, with those brain cells self-destructing.

michael-j-fox Michael J. Fox is a notable person with Parkinson’s disease. Reuters/Mario Anzuoni

The mice who lose their LRRK1 and LRRK2 genes also had shorter lifespans and lower body weights, according to the institute.

Those dopamine-containing neurons that were dying off are the brain cells “most affected by Parkinson’s,” NINDS reported, so the research could hold clues about how to treat it.

Currently, the institute noted, some medical treatments focus on inhibiting LRRK2, but this new research might change that approach.

“Our findings show that LRRK is critical for the survival of the populations of neurons affected by Parkinson’s disease,” Shen said.

The study was published in the journal Neuron.

“Since its discovery, researchers have been trying to define LRRK2 function and how mutations may lead to Parkinson’s disease,” NINDS program director Beth-Anne Sieber said in the statement. “The findings in this paper emphasize the importance of understanding the normal role for genes associated with neurodegenerative disorders.”

In the future, the scientists are looking to study in more detail the effect of deleting mice’s LRRK2 gene.

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