Scientists at the National Institutes of Health (NIH) have uncovered a new batch of genes that may provide breakthrough treatment options for people suffering from Parkinson’s disease, the degenerative disorder of the central nervous system that begins with reduced motor control, and eventually worsens to include neurological decay.
In the new study, NIH researchers combed through 22,000 individual genes in order to arrive at several dozen that they believe could offer therapeutic benefits for patients suffering from Parkinson’s. Through their research, they also found certain genes that may hold the key to diseases of the mitochondria; structures often referred to as the “powerhouses” of the cell, because of their role in producing the cell’s energy in the form of adenosine triphosphate (ATP), through respiration.
“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,” Dr. Richard Youle a researcher at the National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the study, said in a statement.
The study utilized RNA interference — a naturally occurring process scientists have used since 1998 to manipulate a cell’s genes — in order to investigate the effect of turning off nearly 22,000 genes individually. The team was searching for parkin, a protein that swims freely inside the cell and tags damaged mitochondria as waste. Specifically, they were investigating how silencing each gene affected parkin’s ability to tag the mitochondria, a process that, if unfulfilled, leads to an accumulation of the damaged structures inside the cell. Among the dozens they found linked to decreased parkin tagging, the team found at least four, called TOMM7, HSPAI1L, BAG4 and SIAH3, that may act as helpers.
“These genes work like quality control agents in a variety of cell types, including neurons,” said Dr. Youle, adding that some genes, such as TOMM7 and HSPAI1L, inhibited parkin tagging, while others, including BAG4 and SIAH3, enhanced tagging. “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.”
Currently ranked as the 14th leading cause of death in the United States, Parkinson’s affects roughly one million Americans — exceeding the combined diagnoses of multiple sclerosis, muscular dystrophy, and Lou Gehrig’s disease (amyotrophic lateral sclerosis). Approximately 60,000 Americans are newly diagnosed each year, with men roughly one-and-a-half times more likely to have the disorder than women.
Some Parkinson’s cases have been linked to mutations in the genes that code for parkin, a factor that initially prompted researchers to investigate the specific genes responsible for parkin tagging. While the specific mechanisms behind Parkinson’s aren’t well known, researchers speculate genetics and environmental factors play partial roles. The greatest symptoms of Parkinson’s originate in the decreased activity in dopamine-secreting cells in the brain, which result from mitochondria-induced cell death. Sufferers lose motor function and various cognitive processes as the disease worsens.
Being able to pinpoint which genes ultimately regulate this mitochondria function will help scientists develop treatment options that target certain genes specifically, obviating the need for blanket treatments with harsh side-effects.
“This study shows how the latest high-throughput genetic technologies can rapidly reveal insights into fundamental disease mechanisms,” said Dr. Story Landis, director of the NINDS. “We hope the results will help scientists around the world find new treatments for these devastating disorders.”
Source: Hasson S, Kane L, Yamano K. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy. Nature. 2013.