BURDON SANDERSON PRIZE LECTURE: Targeting calcium leak to treat disorders of heart, muscle and brain
Calcium (Ca2+) is a requisite second messenger in all living organisms. From C. elegans to mammals, Ca2+ is necessary for locomotion, bodily functions, and neural activity. However, too much of a good thing can be bad. Intracellular Ca2+ overload can result in loss of function and death. Intracellular Ca2+ release channels evolved to safely provide large, rapid Ca2+ signals without exposure to toxic extracellular Ca2+. Ryanodine receptors (RyRs) are intracellular Ca2+ release channels present throughout the zoosphere. Over the past 35 years, our knowledge of RyRs has advanced to the level of atomic-resolution structures revealing their role in the mechanisms underlying the pathogenesis of human disorders of heart, muscle, and brain. Stress-induced RyR-mediated intracellular Ca2+ leak in the heart can promote heart failure and cardiac arrhythmias. In skeletal muscle, RyR1 leak contributes to muscle weakness in inherited myopathies, to age-related loss of muscle function and cancer-associated muscle weakness, and to impaired muscle function in muscular dystrophies, including Duchenne. In the brain, leaky RyR channels contribute to cognitive dysfunction in Alzheimer’s disease, posttraumatic stress disorder, and Huntington’s disease. Novel therapeutics targeting dysfunctional RyRs are showing promise.
Date: 20 May 2025, 16:00
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: Blakemore Lecture Theatre
Speaker: Professor Andrew R. Marks (Columbia University)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser: Professor David Paterson (University of Oxford)
Organiser contact email address: events@dpag.ox.ac.uk
Host: Professor David Paterson (University of Oxford)
Part of: DPAG Prize Lectures
Booking required?: Not required
Audience: Members of the University only
Editor: Hannah Simm