Navigation Links
Gene-silencing study finds new targets for Parkinson's disease
Date:11/24/2013

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."


'/>"/>

Contact: Christopher G Thomas
thomaschr@ninds.nih.gov
301-435-2264
NIH/National Institute of Neurological Disorders and Stroke
Source:Eurekalert  

Related biology news :

1. New genomic study provides a glimpse of how whales could adapt to ocean
2. Study finds gene network associated with alcohol dependence
3. A study on cell migration provides insights into the movement of cancer cells
4. UT Dallas study: Initial success for new tinnitus treatment
5. Connections in the brains of young children strengthen during sleep, CU-Boulder study finds
6. Women prescribed combination HRT should use caution when taking apigenin supplement, MU study finds
7. Dartmouth-led study shows diet alone can be significant source of arsenic
8. Shadehouses with photoselective nets featured in study of growing conditions
9. Study to identify functions of hypothetical genes in 2 infectious disease pathogens
10. Bone marrow mononuclear stem cells show no new gains in heart function says TIME study
11. Drexel study: Consumers order a less unhealthy meal when the menu has nutritional labeling
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Gene-silencing study finds new targets for Parkinson's disease
(Date:4/5/2017)... , April 5, 2017 Today HYPR ... that the server component of the HYPR platform is ... providing the end-to-end security architecture that empowers biometric authentication ... HYPR has already secured over 15 million users across ... manufacturers of connected home product suites and physical access ...
(Date:3/30/2017)... The research team of The Hong Kong Polytechnic University (PolyU) ... ground breaking 3D fingerprint minutiae recovery and matching technology, pushing contactless ... use in identification, crime investigation, immigration control, security of access and ... ... A research team led by Dr Ajay Kumar ...
(Date:3/24/2017)... The Controller General of Immigration from Maldives Mr. Mohamed ... received the prestigious international IAIR Award for the most innovative high security ... ... Maldives Immigration Controller General, ... picture on the right) have received the IAIR award for the "Most ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 11, 2017 , ... At its national board meeting in ... Sheikh, the co-founder, CEO and chief research scientist of Minnesota-based Advanced Space Technology ... in ARCS Alumni Hall of Fame . ASTER Labs is a technology ...
(Date:10/11/2017)... Wayne. NJ (PRWEB) , ... October 11, 2017 , ... Personal eye wash is a ... rinse one eye at a time. So which eye do you rinse first if a ... you have Plum Duo Eye Wash with its unique dual eye piece. , ...
(Date:10/11/2017)... ... October 11, 2017 , ... Proscia Inc ., ... a Webinar titled, “Pathology is going digital. Is your lab ready?” with Dr. ... best practices and how Proscia improves lab economics and realizes an increase in ...
(Date:10/11/2017)... HILLS, Calif. , Oct. 11, 2017  SkylineDx today ... (ICR) and University of Leeds ... risk-stratify patients with multiple myeloma (MM), in a multi-centric Phase ... University of Leeds is the sponsor ... and ICR will perform the testing services to include high-risk ...
Breaking Biology Technology: