Washington: Researchers have used RNA interference (RNAi) - a natural process occurring in cells that helps regulate genes - to reveal dozens of genes which could 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.
Richard Youle, Ph.D., an investigator at the National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the study, said that they 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.
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.
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.
The researchers then 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.
The study has been published online in journal Nature.