Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
Scientific Community
Become a Member | Sign in
Home>News>This Article

Gene-Silencing Study Finds New Targets for Parkinson’s Disease

Published: Monday, November 25, 2013
Last Updated: Monday, November 25, 2013
Bookmark and Share
NIH study sheds light on treatment of related disorders.

Scientists at the National Institutes of Health have used RNA interference (RNAi) technology to reveal dozens of genes which may represent new therapeutic targets for treating Parkinson’s disease. The findings also may be relevant to several diseases caused by damage to mitochondria, the biological power plants found in cells throughout the body.

“We discovered a network of genes that may regulate the disposal of dysfunctional mitochondria, opening the door to new drug targets for Parkinson’s disease and other disorders,” said Richard Youle, Ph.D., an investigator at the National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the study. The findings were published online in Nature. Dr. Youle collaborated with researchers from the National Center for Advancing Translational Sciences (NCATS).

Mitochondria are tubular structures with rounded ends that use oxygen to convert many chemical fuels into adenosine triphosphate, the main energy source that powers cells. Multiple neurological disorders are linked to genes that help regulate the health of mitochondria, including Parkinson’s, and movement diseases such as Charcot-Marie Tooth Syndrome and the ataxias.

Some cases of Parkinson’s disease have been linked to mutations in the gene that codes for parkin, a protein that normally roams inside cells, and tags damaged mitochondria as waste. The damaged mitochondria are then degraded by cells’ lysosomes, which serve as a biological trash disposal system. Known mutations in parkin prevent tagging, resulting in accumulation of unhealthy mitochondria in the body.

RNAi is a natural process occurring in cells that helps regulate genes. Since its discovery in 1998, scientists have used RNAi as a tool to investigate gene function and their involvement in health and disease.

Dr. Youle and his colleagues worked with Scott Martin, Ph.D., a coauthor of the paper and an NCATS researcher who is in charge of NIH’s RNAi facility. The RNAi group used robotics to introduce small interfering RNAs (siRNAs) into human cells to individually turn off nearly 22,000 genes. They then used automated microscopy to examine how silencing each gene affected the ability of parkin to tag mitochondria.

“One of NCATS’ goals is to develop, leverage and improve innovative technologies, such as RNAi screening, which is used in collaborations across NIH to increase our knowledge of gene function in the context of human disease,” said Dr. Martin.

For this study, the researchers used RNAi to screen human cells to identify genes that help parkin tag damaged mitochondria. They found that at least four genes, called TOMM7, HSPAI1L, BAG4 and SIAH3, may act as helpers. Turning off some genes, such as TOMM7 and HSPAI1L, inhibited parkin tagging whereas switching off other genes, including BAG4 and SIAH3, enhanced tagging. Previous studies showed that many of the genes encode proteins that are found in mitochondria or help regulate a process called ubiquitination, which controls protein levels in cells.

Next the researchers tested one of the genes in human nerve cells. The researchers used a process called induced pluripotent stem cell technology to create the cells from human skin. Turning off the TOMM7 gene in nerve cells also appeared to inhibit tagging of mitochondria. Further experiments supported the idea that these genes may be new targets for treating neurological disorders.

“These genes work like quality control agents in a variety of cell types, including neurons,” said Dr. Youle. “The identification of these helper genes provides the research community with new information that may improve our understanding of Parkinson’s disease and other neurological disorders.”

The RNAi screening data from this study are available in NIH’s public database, PubChem, which any researcher may analyze for additional information about the role of dysfunctional mitochondria in neurological disorders.

“This study shows how the latest high-throughput genetic technologies can rapidly reveal insights into fundamental disease mechanisms,” said Story Landis, Ph.D., director of the NINDS. “We hope the results will help scientists around the world find new treatments for these devastating disorders.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
A Patient’s Budding Cortex — In A Dish?
Networking neurons thrive in 3-D human “organoid”
Friday, May 29, 2015
Drugs that Activate Brain Stem Cells May Reverse Multiple Sclerosis
NIH-funded study identifies over-the-counter compounds that may replace damaged cells.
Tuesday, April 21, 2015
Stem Cell Transplants May Halt Progression of Multiple Sclerosis
NIH-funded study yields encouraging early results.
Tuesday, December 30, 2014
Scientists Sniff Out Unexpected Role for Stem Cells in the Brain
NIH scientists find that restocking new cells in the brain’s center for smell maintains crucial circuitry.
Saturday, October 11, 2014
Suspect Gene Corrupts Neural Connections
“Diseases of synapses” demo’d in a dish - NIH-funded study.
Tuesday, August 19, 2014
Early Treatment Benefits Infants with Severe Combined Immunodeficiency
NIH-funded study identifies factors contributing to successful stem cell transplants.
Friday, August 01, 2014
Stem Cells Form Light-Sensitive 3-D Retinal Tissue
Researchers induced human stem cells to create a 3-D retina structure that responds to light. The finding may aid the study of eye diseases and could eventually lead to new therapies.
Tuesday, June 24, 2014
Stem Cell Therapy Rebuilds Heart Muscle in Primates
Human embryonic stem cells used to regenerate damaged primate hearts.
Tuesday, May 13, 2014
Too Much Protein May Kill Brain Cells As Parkinson’s Progresses
NIH-funded study on key Parkinson’s gene finds a possible new target for monitoring the disease.
Friday, April 11, 2014
NeuroBioBank Gives Researchers One-Stop Access to Post-Mortem Brains
The NIH is shifting from a limited funding role to coordinating a Web-based resource for sharing post-mortem brain tissue, a move which is expected to expedite research on brain disorders.
Tuesday, December 03, 2013
Epigenetic Clock Marks Age of Human Tissues and Cells
The age of many human tissues and cells is reflected in chemical changes to DNA. The finding provides insights for cancer, aging, and stem cell research.
Tuesday, November 05, 2013
NIH Scientists Pursue New Therapies to Improve Rare Disease Drug Development
Projects selected for potential to treat specific rare diseases.
Friday, September 13, 2013
Stem Cells Discovered in Deadly Parasitic Flatworms
The study was described in Nature on February 28, 2013.
Friday, March 15, 2013
New Type of Pluripotent Cell Discovered In Adult Breast Tissue
Human body carries personalized “patch kit," Say UCSF scientists.
Tuesday, March 05, 2013
Scientific News
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
CRI Identifies Emergency Blood-formation Response
Researchers report that when tissue damage occurs, an emergency blood-formation system activates.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
Promise of Newborn Stem Cells to Revolutionize Clinical Practice
In this article Shweta Sharma, PhD, discusses the potential of an Umbilical Cord Blood bank as an untapped source of samples for research and clinical trials.
The Life Story of Stem Cells
A model analyses the development of stem cell numbers in the human body.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Advancing Genome Editing of Blood Stem Cells
Genome editing techniques for blood stem cells just got better, thanks to a team of researchers at USC and Sangamo BioSciences.
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Towards Patient-Specific Drug Screening
A new breakthrough by the 3D stem cell printing team at Heriot-Watt could pave the way to individually tailored drug testing regimes, both reducing the need for animal testing and ensuring that patients receive drugs which are most effective for their individual needs.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos