Parkinson's gene initiates disease outside of the brain

March 21, 2018, Thomas Jefferson University

Until very recently, Parkinson's had been thought a disease that starts in the brain, destroying motion centers and resulting in the tremors and loss of movement. New research published this week in the journal Brain, shows the most common Parkinson's gene mutation may change how immune cells react to generic infections like colds, which in turn trigger the inflammatory reaction in the brain that causes Parkinson's. The research offers a new understanding of Parkinson's disease.

"We know that brain cells called microglia cause the inflammation that ultimately destroys the area of the brain responsible for movement in Parkinson's," said Richard Smeyne, PhD, Director of the Jefferson Comprehensive Parkinson's Disease and Movement Disorder Center at the Vickie and Jack Farber Institute for Neuroscience. "But it wasn't clear how a common inherited mutation was involved in that process, and whether the mutation altered microglia."

Together with Dr. Smeyne, first author Elena Kozina, PhD, looked at the mutant version of the LRRK2 gene (pronounced 'lark'). Mutations in the LRRK2 gene are the most common cause of inherited Parkinson's disease and are found in 40 percent of people of North African Arab descent and 18 percent of people of Ashkenazi Jewish descent with Parkinson's. However there's been controversy around the exact function of the LRRK2 gene in the brain.

"We know that is not enough to cause the disease," said Dr. Kozina, Post-Doctoral student at Jefferson (Philadelphia University + Thomas Jefferson University). "We know that twins who both carry the mutation, won't both necessarily develop Parkinson's. A second 'hit' or initiating event is needed."

Based on his earlier work showing that the flu might increase risk of Parkinson's disease, Dr. Smeyne decided to investigate whether that second hit came from an infection. Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent—the outer shell of bacteria, called lippopolysaccharide (LPS) - that causes an . LPS itself does not pass into the brain, nor do the it activates, which made it ideal for testing whether this second hit was acting directly in the brain.

When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a "cytokine storm," with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.

Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the region involved in movement.

"Although more tests are needed to prove the link, as well as testing whether the same is true in humans, these findings give us a new way to think about how these could cause Parkinson's," said Dr. Smeyne. "Although we can't treat people with immunosuppressants their whole lives to prevent the disease, if this mechanism is confirmed, it's possible that other interventions could be effective at reducing the chance of developing the ."

Explore further: Research discovers possible link between Crohn's and Parkinson's in Jewish population

More information: Elena Kozina et al, Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo, Brain (2018). DOI: 10.1093/brain/awy077

Related Stories

Research discovers possible link between Crohn's and Parkinson's in Jewish population

January 11, 2018
Mount Sinai Researchers have just discovered that patients in the Ashkenazi Jewish population with Crohn's disease (a chronic inflammatory of the digestive system) are more likely to carry the LRRK2 gene mutation. This gene ...

Early intervention may be possible for Parkinson's disease

December 9, 2016
One of the largest post-mortem brain studies in the world has confirmed that a protein (LRRK2) associated with the development of Parkinson's disease is increased in the pre-symptom stages, leading researchers to believe ...

Infection with seasonal flu may increase risk of developing Parkinson's disease

May 30, 2017
Most cases of Parkinson's have no known cause, and researchers continue to debate and study possible factors that may contribute to the disease. Research reported in the journal npj Parkinson's Disease suggests that a certain ...

Scientists observe tremors associated with Parkinson's disease in fruit flies

December 6, 2017
Scientists say they have a better understanding of the tremors commonly associated with Parkinson's disease after observing the movements in fruit flies.

Recommended for you

A common anti-inflammatory therapy may help reduce risk of developing Parkinson's disease

April 23, 2018
A recent study from researchers at the Icahn School of Medicine at Mount Sinai provides new insights into a link between inflammatory bowel disease (IBD) and Parkinson's disease, and may have significant implications for ...

Eating fish could prevent Parkinson's disease

April 23, 2018
A new study from Chalmers University of Technology, Sweden, shines more light on the link between consumption of fish and better long-term neurological health. Parvalbumin, a protein found in great quantities in several fish ...

Key factor in development of Parkinson's disease identified

April 20, 2018
A molecule has been identified that appears to play an important role in the development of Parkinson's disease, a debilitating disease that affects millions of people around the world.

Augmented reality app may aid patients with Parkinson's

April 12, 2018
It's appropriate that during Parkinson's Awareness Month, a team of Rice University seniors will show how augmented reality may help patients with the disease.

Are people with Parkinson's disease depressed or demoralized?

April 4, 2018
People with Parkinson's disease who show signs of depression may actually have a condition called demoralization, according to a study published in the April 4, 2018, online issue of Neurology, the medical journal of the ...

Mobile apps could hold key to Parkinson's research, care

March 27, 2018
A new study out today in the journal JAMA Neurology shows that smartphone software and technology can accurately track the severity of the symptoms of Parkinson's disease. The findings could provide researchers and clinicians ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.