Study first to link mitochondrial dysfunction and alpha-Synuclein multiplication in human fibroblasts

October 6, 2011, IOS Press

A new study in the Journal of Parkinson's Disease shows for the first time the effects of α-Synuclein (α-syn) gene multiplication on mitochondrial function and susceptibility to oxidative stress in human tissue. Mitochondrial dysfunction has been frequently implicated in the neurodegenerative process that underlies Parkinson's disease, but the basis for this has not been fully understood.

Investigators from The Parkinson's Institute in Sunnyvale, CA, evaluated skin fibroblasts from a patient with parkinsonism carrying a triplication in the α-syn gene (SNCA). The cells showed a significant decrease in cell growth compared with healthy controls. "Our results in patient-derived fibroblasts were remarkably similar to overexpression experiments in cell lines and animal models. We detected a decrease in ATP production, a reduction in mitochondrial membrane potential, and a reduction in complex I activity," commented Birgitt Schüle, MD, Assistant Professor, The Parkinson's Institute. Furthermore, these fibroblasts proved to be more sensitive to the effects of the neurotoxin and herbicide paraquat compared to controls.

Mitochondrial function and cellular damage were partially rescued after siRNA knockdown of α-synuclein in after paraquat treatment. "We observed a significant increase in membrane potential and cellular ATP synthesis as well as a decrease in LDH release, supporting the hypothesis that α-synuclein expression levels are directly related to mitochondrial dysfunction," said Dr. Schüle.

According to Dr. William Langston, the Scientific Director and CEO of The Parkinson's Institute, and a co-author on the paper, these results are particularly exciting because they directly link a-syn over-expression and mitochondrial dysfunction in tissue from a parkinsonian patient. "One of the keys to unraveling this incurable and progressive disease is to solve the relationship between a-syn and mitochondrial dysfunction. In these results, we may have the first such link in human tissue," Langston said.

Explore further: Rare genetic disorder provides unique insight into Parkinson's disease

More information: The article is "Mitochondrial Dysfunction in Skin Fibroblasts from a Parkinson's Disease Patient with an alpha-Synuclein Triplication" by Sally K. Mak, Deepika Tewari, James W. Tetrud, William J. Langston, and Birgitt Schüle. Journal of Parkinson's Disease. 1(2). DOI:10.3233/JPD-2011-11205

Related Stories

Rare genetic disorder provides unique insight into Parkinson's disease

June 23, 2011
Massachusetts General Hospital investigators appear to have found the mechanism behind a previously reported link between the rare genetic condition Gaucher disease and the common neurodegenerative disorder Parkinson's disease. ...

Seeds of destruction in Parkinson's disease: Spread of diseased proteins kills neurons

October 5, 2011
New research suggests that small "seed" amounts of diseased brain proteins can be taken up by healthy neurons and propagated within them to cause neurodegeneration. The research, published by Cell Press in the October 6 issue ...

Recommended for you

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

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.