Universitat Autònoma de Barcelona
Invited by Luigi Bellochio (Neurocentre Magendie)
Different neurons, one disease: Parsing cell-type specific neuronal programs to treat mitochondrial disease
Mutations in genes encoding mitochondrial proteins result in mitochondrial disease (MD), a diverse group of orphan pathologies leading to neuromuscular deficits and death. Neurons are commonly affected in MD. However, there is a marked cell-specificity on the neuronal vulnerability to mitochondrial dysfunction, and the underlying mechanisms leading to neuronal demise remain unknown, limiting our ability to develop effective treatments for these pathologies. Combining mouse genetics with novel molecular biology tools we have identified several neuronal populations particularly susceptible to mitochondrial dysfunction in a mouse model lacking the mitochondrial complex I subunit Ndufs4 (Ndufs4KO mice), one of the best mouse models of mitochondrial disease. Using cell-type specific approaches, we have elucidated several concerted molecular mechanisms underlying neuronal demise in vulnerable neurons. Finally, we provide evidence of the efficacy of cannabidiol, by targeting these pathways, can be a novel treatment for MD.
Albert Quintana is an Associate Professor of the Department of Cell Biology, Physiology and Immunology. He earned a Bachelor in Science in Biology (Biomedicine) in 2001 and a PhD in Neuroscience in 2007, both from the Universitat Autònoma de Barcelona. During his PhD focused on the role of cytokines in the development of neuropathology and neuroinflammation in traumatic brain injury. As a postdoc (2008-2013), he joined Dr. Richard Palmiter lab at the University of Washington in Seattle, where he was the lead scientist developing and characterizing a mouse model of mitochondrial disease (Leigh Syndrome). In 2013 he was appointed Assistant Professor in the Department of Pediatrics (University of Washington) and group leader at the Seattle Children’s Research Institute. In 2015 he returned to the Universitat Autònoma de Barcelona as a Ramón y Cajal investigator and ERC grantee (Starting Grant). His research focuses on using a multi-level approach and to develop new tools to identify the molecular determinants of neuronal susceptibility to mitochondrial disease. He has authored over 50 research articles and 2 book chapters.