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Monday, June 13, 2016

Scientists Discover New Genetic Cause of Parkinson’s Disease (More Information on TMEM230)

 June 13, 2016
Kristen Thometz

More Information:

Researchers discovered that TMEM230 encodes a protein that extends across the membrane of synaptic vesicles, which are tiny sacks that store neurotransmitters before they are released to other cells. (Wikimedia Commons)

For more than 20 years, researchers at Northwestern University have collaborated with a global network of scientists to try and unravel the mysteries of Parkinson's disease. A study published this month in Nature Genetics shares an important discovery from that research. Not only does it offer insight into how the disease develops, it could change the way the disease is treated in the future.
There’s no cure for Parkinson’s disease, but researchers have learned that mutations in a gene called TMEM230 have been shown to cause the disease, the study states.
“It was completely surprising,” said Dr. Teepu Siddique, a professor at Northwestern University Feinberg School of Medicine who was one of the study’s researchers. “Its function was unknown.”
The discovery is significant because about 15 to 25 percent of Parkinson’s disease cases are believed to be caused by genetics, according to the Parkinson’s Disease Foundation. This is the third gene to be linked to the neurodegenerative disease that is characterized by symptoms such as tremors, stiffness and slowness of movement.
“It’s a progressive disease,” Siddique said. “There are symptomatic treatments that relieve symptoms—mainly the motor symptoms.”
Typically, Parkinson’s disease occurs late in life, with the incidence of occurrence increasing with age. Diagnosis before the age of 45, such as the late Muhammad Ali’s at the age of 42, is very rare, according to Siddique.
Discovering Gene TMEM230
This new genetic link came with its own mystery.
“This gene, it encodes a protein that has never been investigated before,” Siddique said.
Researchers discovered that TMEM230 encodes a protein that extends across the membrane of synaptic vesicles, which are tiny sacks that store neurotransmitters before they are released to other cells.
“We found that it is part of a membrane that surrounds synaptic vesicles that release the neurotransmitters that are decreased in this particular disease,” he said. “We think this is the first identification of a cross-membrane protein of synaptic vesicles of Parkinson’s disease.”
In the video below, learn more about how neurotransmission works.

We think that understanding the biology of this protein and how it moves, the movement of synaptic vesicles and other vesicles in the neurons will help us to devise rational therapies,” Siddique said.
“We think that these mutations in this protein slow down the transport of these vesicles and you get a logjam of protein buildup around these vesicles, and the cell starts to suffer and eventually dies.”
The 20-year project began in the early 1990s when Siddique and Dr. Ali Rajput, co-author of the study and an expert in Parkinson’s disease, identified 15 family members who had typical symptoms of Parkinson’s disease. Researchers performed a genome-wide analysis of 65 of the family members, including 13 with Parkinson’s disease.
“This was before there was sequencing techniques that could be done across the genome. ... Eventually, after a long painstaking set of time we were able to find the location of the gene, track the mutation of the gene itself, and we knew where to look and it was on the short arm of chromosome 20,” Siddique said. “We narrowed it down from there and by that time exome sequencing came about, and we were able to sequence the individuals in the family who had the disease and found a common mutation in this region.”
After verifying their findings, researchers compared the genetic differences between family members who had the disease and those who didn’t. The process was repeated with additional families in North America and China, and researchers found mutations in TMEM230 in people with Parkinson’s disease.
“We think this is an epigenetic mutation that can happen across the globe,” Siddique said, adding it appears that the environment and ethnicity have little impact on the disease or mutation. “We’re excited about the changes that can come from this work and our understanding of the disease.
Future research should build upon this knowledge and explore how TMEM230 genetic mutations cause the disease in animal and cellular models, Siddique said. 
If researchers found a way to normalize the movements of vesicles and optimize them, “we could possibly alter the course of the disease or stop it,” Siddique said. “Those are the sorts of things that we will be testing now or devising experiments to test.”
http://chicagotonight.wttw.com/2016/06/13/scientists-discover-new-genetic-cause-parkinson-s-disease

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