Numbing intraneuronal Tau levels to prevent neurodegeneration in tauopathies
Dr.
Montreal Clinical Research Institute (IRCM)
Event Information
Host
Manitoba Neuroscience Network
Duration
70 minutes
Abstract
Intraneuronal accumulation of the microtubule associated protein Tau is largely recognized as an important toxic factor linked to neuronal cell death in Alzheimer’s disease and tauopathies. While there has been progress uncovering mechanisms leading to the formation of toxic Tau tangles, less is known about how intraneuronal Tau levels are regulated in health and disease. Here, I will discuss our recent work showing that the intracellular trafficking adaptor protein Numb is critical to control intraneuronal Tau levels. Inactivation of Numb in retinal ganglion cells increases monomeric and oligomeric Tau levels and leads to axonal blebbing in optic nerves, followed by significant neuronal cell loss in old mice. Interestingly, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels by promoting exocytosis of monomeric Tau. In TauP301S and triple transgenic AD mouse models, expression of Numb-72 in RGCs reduces the number of axonal blebs and prevents neurodegeneration. Finally, inactivation of Numb in TauP301S mice accelerates neurodegeneration in both the retina and spinal cord and leads to precocious paralysis. Taken together, these results uncover Numb as a essential regulator of Tau homeostasis in neurons and as a potential therapeutic agent for AD and tauopathies.
Topics
Related Seminars
Deciphering the Dynamics of the Unconscious Brain under General Anesthesia
Stanford Neurosciences Seminar Series talk by Emery Brown (Massachusetts Institute of Technology, Neuroscience Statistics Research Lab) on deciphering the dynamics of the unconscious brain under…
Engineering human myelination in vitro: Mechanobiologically compatible platforms for CNS drug discovery
UCL Department of Neuroinflammation Seminar by Professor Emad Moeendarbary (Professor of Cell Mechanics and Mechanobiology, UCL Mechanical Engineering) on how biophysical factors such as substrate…
Colloquium on the Brain and Cognition with Christopher Harvey, PhD, Harvard University
Picower Institute Colloquium on the Brain and Cognition featuring Christopher Harvey, PhD, of Harvard University, held in Singleton Auditorium (46-3002) at MIT Building 46, 43 Vassar Street.
Related Job Opportunities
PhD Studentship: Mitochondrial Metabolism and Novel Therapeutic Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (Fixed Term)
Supervisors: Professor Andrew Murray, Department of Physiology, Development and Neuroscience, University of Cambridge Dr Ross Lindsay, Novo Nordisk Funding: Fully funded PhD studentship (Home/UK…
Research Associate (Fixed Term)
We seek a highly motivated Postdoctoral Research Associate to join the laboratory of Professor Kathy Niakan. We are based in the Loke Centre for Trophoblast Research (LCTR), in the Department of…
Research Assistant/Associate (Fixed Term)
Applications are invited for a postdoctoral research associate position to study the neural mechanisms of visual learning in mice, in the laboratories of Professor Ole Paulsen and Dr Jasper Poort…