New study may aid treatment and prevention of tremors in Parkinson’s Disease

International research team, including UNR Med scientist, collaborate on new insights for improved treatments for patients

Brian Perrino, Ph.D., associate professor, department of physiology and cell biology, is part of an international research team which has made a discovery, identifying major implications for understanding disorders of the nervous system associated with tremor, such as Parkinson's Disease. Pictured, Perrino uses a Revolve microscope to analyze the protein-protein interaction between LINGO1 and BK in HEK293 cells. The immunofluorescence from the proximity ligation assay shows us the numbers of LINGO1 and BK interactions at different levels of LINGO1 expression. UNR Med photo by Brin Reynolds.  

A new study released from an international research team has made a discovery, identifying major implications for understanding disorders of the nervous system associated with tremor, such as Parkinson's Disease. The new insights could support the quest for better treatments and improve the lives of people living with debilitating movement disorders.

Parkinson's Disease is a slowly progressive neurodegenerative movement disorder, affecting nearly one million people in the United States, with approximately 60,000 Americans diagnosed each year. The Global Burden of Disease estimates that 6.2 million individuals worldwide have Parkinson's disease. Currently, there is no cure.  

The Dundalk Institute of Technology (DkIT) in Ireland is leading an international team of investigators from the Dundalk Institute, University of Edinburgh in Scotland, Queen's University of Belfast in Northern Ireland and the University of Nevada, Reno School of Medicine (UNR Med) in the U.S., to study the problem of neurodegenerative movement disorders from multiple approaches.  

The study is receiving funding through the European Union (EU) and has recently been published in the leading scientific journal, Proceedings of the National Academy of Science of the United States of America (PNAS).  

There are three main symptoms to Parkinson's Disease, including tremor (shaking), slowness of movement and muscle stiffness. As the disease progresses, people may have difficulty walking and talking. Cognitive and behavioral changes, sleep problems, depression, memory difficulties, and fatigue may also develop. Patients often require around-the-clock nursing care.  

These symptoms are caused by damage to neurons in a small area of the brain located in the cerebellum. In patients with Parkinson's, these neurons gradually become damaged and eventually die. Unlike many other cells in the body, nerve cells cannot undergo cell division and make new nerve cells.   

"Previous research has determined that a protein called LINGO1, which helps control movement, is abnormally overexpressed in patients with Parkinson's disease and essential tremor, while other studies showed that a loss of another protein, the BK ion channel, in these cerebellar neurons results in tremor and movement disorders," said Brian Perrino, Ph.D., associate professor, department of physiology and cell biology at UNR Med and research investigator on the project.

Perrino expanded that "these two findings were previously thought to be unrelated. We put these two findings together and showed that LINGO1 inhibits the activity of BK channels, LINGO1 also reduces the expression of BK channels, the brains of Parkinson's disease patients have higher levels of LINGO1, and LINGO1 is assembled with BK channels in the brains of Parkinson's disease patients."  

"This new knowledge has major implications for our understanding of neurodegenerative disorders associated with tremor, such as Parkinson's Disease and essential tremor. These findings represent a breakthrough in our understanding of the causes of tremor in Parkinson's Disease," said Perrino.  

Perrino explained that "what is particularly exciting is that by developing innovative therapeutics and pharmacological agents that block the interaction of LINGO1 with the BK channel, the loss of activity in the brain could be prevented, improving the lives of people living with debilitating movement disorders in the future."  

Mark Hollywood, Ph.D., professor, molecular physiology at the Dundalk Institute and project lead said, "By bringing together an international team with complementary skills, this multi-disciplinary study promises to advance research and reveal new ways to help reduce the motor disorders associated with major disorders of the human brain."  

"UNR Med is immensely proud to have Dr. Perrino be part of this this important international research collaboration. We congratulate the entire research team for their work in advancing the knowledge needed to find ways to improve patients' lives, said UNR Med Dean Thomas L. Schwenk, M.D. Dr. Perrino's contributions to the project are a testament to the global research capabilities at UNR Med."

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The University of Nevada, Reno School of Medicine, Nevada's first public medical school, is a community-based, research-intensive medical school with a statewide vision for a healthy Nevada. Established in 1969, UNR Med is improving the health and well-being of all Nevadans and their communities through excellence in student education, postgraduate training and clinical care, research with local, national and global impact and a culture of diversity and inclusion.

Released: Tuesday March 3, 2020 @ 6:00 AM