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New targets in Parkinson’s disease found

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With the help of a new technology, called RNA interference, researchers at the National Institutes of Health have revealed new genes that could be used as therapeutic targets for the treatment of Parkinson’s disease. The new study provides new information not only about Parkinson’s disease but also about other diseases caused by mitochondrial dysfunction. Richard Youle, Ph.D., an investigator at the National Institutes of Neurological Disorders and Stroke (NINDS ), and the leader of the study  said they discovered a network of genes that control dysfunctional mitochondria and which could therapeutic targets in the treatment of Parkinson’s disease.

Mitochondria are essential organelles in cell metabolism as mitocondria generate the main energy source of the cell: adenosine triphosphate.  Genes that control the proper functioning of the mitochondria are involved in many neurological diseases such as Parkinson’s disease, Charcot Marie Tooth disease or ataxia. Some cases of Parkinson’s disease are related to mutations in genes encoding for parkin, a protein that removes damaged mitochondria. Mutations in the gene coding for parkin alters cellular metabolism and leads to accumulation of damaged mitochondria in the cell.

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The team of researchers from the National Institutes of Health used iRNA  to silence over 22,000 genes in the human body. The researchers wanted to see the effect of silencing these genes on parkin function and how does this affects mitochondria. For the study, researchers used iRNA to see which genes help parkin to tag mitochondria. It seems that there are at least four genes involved in parkin tag: TOMM7, HSPAI1L, BAG4 and SIAH3; the first two, when inhibited, block parkin tag, while the last two, when switched off, increase parkin tag. The levels of certain proteins in cells are controlled by a process called ubiquitination, and studies have shown that there are many genes that are responsible for ubiquitination or that encode for proteins involved in mitochondrial metabolism.

Researchers have used the induced pluripotent stem cell technology to create nerve cells from  skin cells and then tested one of these genes in the human nerve cells. It seems that blocking TOMM7  inhibits parkin tag. Story Landis, Ph.D., director of the NINDS, said that the study shows that the latest high- throughput genetic technologies can quickly reveal fundamental mechanisms behind the disease. These results have prompted the researchers to think that these genes could be therapeutic targets in the treatment of certain neurological diseases. “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” researchers said.