Dr. David Park has spent countless hours exploring how deactivating a gene impacts the way a cell handles the very nutrients it needs for its own survival and proper function. To Park and his research team, it’s an essential piece of the puzzle that is Parkinson’s disease.
Parkinson’s affects 10 million people worldwide, causing a degeneration of the body’s nerve cells and a progressive loss of motor control.
“New therapies are desperately needed to ease the symptoms of Parkinson’s and slow its progress,” he says. “It devastates not only the body, but the health care system as well.”
A team of researchers from the University of Ottawa Faculty of Medicine, led by Dr. Park, has delineated the mechanism by which a gene mutation leads to a form of Parkinson’s disease—namely, the loss of the PINK1 gene. Their findings were published today in Nature Communications, of the highly prestigious Nature family of journals.
Under the collaborative umbrella of the uOttawa Brain and Mind Research Institute (uOBMRI), past papers from Dr. Park and fellow researchers have shown PINK1 to be associated with Parkinson’s. However, this week’s paper marks a deeper understanding of the molecular mechanisms behind it.
Mitochondria are the organelles that process nutrients within a cell, including calcium. Dr. Park’s team found that a protein in the PINK1 gene modifies mitochondrial protein LETM1, a process that plays a critical role in calcium transport in mitochondria. Deactivation of the PINK1 gene—knocking the gene out of mouse models mimics a natural mutation in humans—causes dysfunction of LETM1. This interrupts mitochondria’s normal processing of calcium and leads to brain cell death.
By identifying the specific mechanism causing a cell to mishandle calcium, new targets for drugs have been revealed, opening doors for potential new treatments for Parkinson’s. Five years of research have culminated in these results which En Huang, research associate in the Faculty’s Department of Cellular and Molecular Medicine and co-author of the paper, confirms can proceed to new avenues of drug testing.
“We’ve uncovered a novel molecular pathway in the pathogenesis of Parkinson’s,” Huang says. “Essentially, this means we’ve identified potential targets for new drugs.”
Several top researchers from the uOBMRI had a hand in the collaborative efforts of the paper. Dr. Park himself is director of the Institute; joining him as authors, among others, are Dr. Daniel Figeys, Chair of the Department of Biochemistry, Microbiology and Immunology, and Dr. Ruth Slack, interim vice-dean of research of the Faculty of Medicine and recently elected Fellow of the Royal Society of Canada.
“I’m proud of the excellent paper put together by my team,” says Dr. Park. “It’s work like this and our collaborations with other researchers here in Ottawa that help cement the uOBMRI’s international reputation as a centre of excellence.”
Source of Text: University of Ottawa
Original Research Article:
PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. En Huang, Dianbo Qu, Tianwen Huang, Nicoletta Rizzi, Wassamon Boonying, Dorothy Krolak, Paolo Ciana, John Woulfe, Christine Klein, Ruth S. Slack, Daniel Figeys & David S. Park. Nature Communications 8, Article number: 1399 (2017) doi:10.1038/s41467-017-01435-1