News ArchivesRead News
A Common Mutation Behind Parkinson's May Have Other Side-Effects
Tuesday August 06, 2013
A Mutation of the LRRK2 Gene Prevents Protein Recycling
The Jewish Daily Forward - Recycling for the health of our planet is well understood. But recycling to keep our bodies going? Scientists are finding that the recycling that takes place within the body’s trillions of cells every day plays a key role in aging and disease. It is also at the center of recent findings regarding Parkinson’s Disease and the genes that have been linked to it in Ashkenazi Jews.
A study published in March in Nature Neuroscience reported that mutations on the LRRK2 gene, which is responsible for approximately 15% of Parkinson’s among Ashkenazi Jews, leads to the malfunctioning of a disposal system in the cell that recycles old proteins and breaks them down into their component parts for reuse.
“In all the cells in your body there are systems for eliminating damaged proteins. This cleaning happens daily and it is important that it do so,” said lead author Ana Maria Cuervo of the Albert Einstein College of Medicine in the Bronx. “What we found is that the LRRK2 protein just happens to be blocking the cleaning system.”
Patients with Parkinson’s, a neurodegenerative disease marked by tremors, slowed movement, gait disruptions and balancing difficulties, all have a buildup of abnormal clumps of proteins, or Lewy bodies, in their brain cells. The main constituent is a protein called alpha-synuclein.
For many years, Parkinson’s was not thought to have a genetic basis. But over the past 15 years, researchers have identified a host of genes associated with it. The most common is the LRRK2 gene, identified in 2004. Two years later, one of the mutations on LRRK2, called G2019S, was identified as a risk factor for Parkinson’s in Ashkenazi Jews. Still, the link between mutations on LRRK2, which give rise to abnormal LRRK2 proteins, and the buildup of alpha-synuclein remained a mystery.
Now Cuervo, professor of developmental and molecular biology, chair for the study of neurodegenerative diseases and co-director of the Institute for Aging Research at Einstein, thinks she may have found some answers.
“The cellular cleaning system in all of us declines with age,” said Cuervo. This recycling system, or autophagy, occurs in cellular structures called lysosomes that can be pictured like tiny vacuums with many ports of entry through which proteins are sucked up and broken down, she explained. The ports vary in nature and a protein’s properties will determine which port it can pass through. As we age, more and more of the ports lose function and become disabled so that each lysosome has fewer and fewer ports available for proteins and other debris to pass through — and more waste accumulates inside the cell.
“The normal LRRK2 protein passes easily into the vacuum,” said Cuervo, “But the mutation changes the shape of LRRK2 enough so that it gets stuck and covers the mouth of the vacuum, blocking entry to other proteins, most specifically alpha-synuclein.” This is how a mutation in LRRK2 leads to a buildup of alpha-synuclein.
Bloch, T. (6 Aug 2013). The Jewish Daily Forward. A Common Mutation behind Parkinson's Disease May Have Other Side-Effects. www.forward.com
Recent NewsSep 12 - Australian Researchers Develop New Diagnostic Tool to Spot Early Signs of Parkinson’s
Sep 11 - GeneFo Webinar to Focus on Using Humor to Manage Parkinson’s Disease
Sep 6 - Parkinson’s and the ‘D’ word
Sep 6 - Compounds in Asthma Drugs Might Be Used as Parkinson’s Treatment
Sep 5 - AstraZeneca Joins Takeda, Berg to Advance Development of Parkinson’s Disease Therapies
Sep 1 - Stem Cell Transplant Trial in Parkinson’s Patients Planned After Test in Japan Succeeds in Monkeys
Sep 1 - Titan to Start Phase 1/2 Study of Subdermal Implant to Deliver Requip to Parkinson’s Patients
Aug 30 - FDA Refuses Acorda’s Inbrija New Drug Application Due to Manufacturing Questions
Aug 23 - Support Groups: Are They for You?
Aug 22 - Internet Visits with Parkinson’s Specialist Can Be as Effective as In-person Visits, Trial Finds
Aug 21 - Cavion’s New CMO to Lead Cav3 Platform Development for Neurological Diseases
Aug 15 - Singing Helps Early-stage Parkinson’s Patients Retain Speech, Respiratory Control, Studies Show
Aug 14 - 16 Tips to Increase Your Mobility Confidence While Living With Parkinson’s Disease
Aug 10 - Boxers are fighting back against Parkinson’s
Aug 9 - Parkinson’s Experiment to Be Aboard Next Flight to International Space Station
Aug 9 - Parkinson’s Disease and Sleeping with the Enemy
Aug 7 - The Importance of Oral Health in Parkinson’s Disease
Aug 7 - Researchers Gain Better Insight Into Alpha-Synuclein’s Role in Parkinson’s Disease
Jul 31 - New Digital Cognitive Assessment Tool Receives Positive FDA Review
Jul 20 - Parkinson’s DREAM Challenge Uses Mobile Sensor Data to Monitor Health Based on Movement