BEGIN:VCALENDAR VERSION:2.0 PRODID:https://github.com/derhansen/sf_event_mgt METHOD:PUBLISH BEGIN:VEVENT UID:859-96@www.leopoldina.org CLASS: PUBLIC SUMMARY:The Role of Functional Prion-Like Proteins in the Persistence of Me mory: A Perspective DESCRIPTION:Prions are proteinaceous infectious agents that were discovered in the 1980s by Stanley Prusiner while studying Creutzfeldt-Jakob disease (Prusiner, 1982). Prusiner found that prion proteins exist in two conformat ions soluble and aggregated. The transition between these forms occurs spon taneously. The aggregate conformation is self-perpetuating, pathogenic and kills cells. Soon prion proteins were found to contribute to other neurodeg enerative disorders in people, including Kuru, Transmissible Spongiform Enc ephalopathies, as well as Bovine spongiform encephalopathy in cows (Prusine r 1994; Aguzzi and Weissmann 1998). There is now a growing consensus that s imilar prion-like, self-templating mechanisms underlie a variety of neurode generative disorders including Amyotrophic Lateral Sclerosis, Alzheimer's d isease, Parkinson’s disease, and Huntington's disease (Polymenidou and Clev eland, 2012). Not all prions, however, appear to be disease producing. In 2003 Kandel together with Kausik Si discovered a prion-like protein in the nervous system of the marine snail Aplysia, whose aggregated and self-perpe tuating form contributes to the maintenance of long-term changes in synapti c efficacy. In earlier work Kandel and Kelsey Martin had found that long-te rm memory in Aplysia is synapse-specific. Moreover the synapse-specific lon g-term memory requires local protein synthesis at the activated synapse. Th is local protein synthesis serves two functions: \n\nit provides a compon ent of the mark at the activated synapse and thereby confers synapse specif icity andit stabilizes the synaptic growth associated with long-term facili tation. \n\n Kandel and Kausik Si next found that this synaptic protein sy nthesis is regulated by a neuron-specific isoform of cytoplasmic polyadenyl ation element binding protein (CPEB) in an activity-dependent manner. Aplys ia CPEB protein is upregulated locally at activated synapses, and it is nee ded not for the initiation, but only for the stable maintenance of long-ter m facilitation. They next explored the nature of CPEB and found it to have prion-like properties. Prion proteins have the unusual capacity to fold int o two functionally distinct conformations, one of which is self-perpetuatin g. When yeast prion proteins switch state, they produce heritable phenotype s. Kandel and Kausik Si found similar prion-like properties in a neuronal m ember of the CPEB family, which regulates mRNA translation at the synapse. Compared to other CPEB family members, the neuronal protein has an N-termin al extension that shares characteristics of yeast prion-determinants: a hig h glutamine content and predicted conformational flexibility. When fused to a reporter protein in yeast, this region confers upon it the epigenetic ch anges in state that characterize yeast prions. The researchers found that i t is the conversion of CPEB to a prion-like state at the stimulated synapse s that maintains long-term synaptic changes associated with memory storage. Recently Kandel and Kausik Si have extended this work in two directions: \n\nthey searched for and found CPEB-3 as a homolog of ApCPEB in the mammal ian brain and found that CPEB-3 has prion-like properties and is activated by Neuralized, an ubiquitin hydrolase.they next looked for a second example of prions in the mammalian brain, and found a completely new candidate – T IA (T-cell intracellular antigen). TIA has classic prion properties in yeas t and serves as part of the cellular response to systemic stress. TIA serve s as a sex-specific protective factor in PTSD and does so in female mice on ly. \n\n In his talk Kandel will consider the emerging biology of function al prions and their various roles in brain and behavior. Photo: Eve Vagg, C olumbia University \n\nRegistration and further information\n\nThe lecture addresses a professional audience and is held in English. For registration, please use the following link: The event ist fully booked.\n\nContact\n\nD r Katja PatzwaldtScientific OfficerTel.: +40 (0)30 203 8997-431E-Mail: katj a.patzwaldt@leopoldina.org\n\nEric R. Kandel\n\nThe neuroscientist and Leop oldina member since 1989 won the Nobel Prize for Physiology or Medicine in the year 2000, sharing it with Arvid Carlsson and Paul Greengard. The Nob el committee honoured “their discoveries concerning signal transduction in the nervous system”. Memory and learning have been key research interests to Eric Kandel for his entire academic life.Kandel is the Director of the Kavli Institute for Brain Science at Columbia University, Senior Investig ator at the Howard Hughes Medical Institute and Co-Director of the Mortime r B. Zuckerman Mind Brain Behavior Institute. He has been awarded more th an 20 honorary doctorates and he is member of many national academies of s cience, including the ones of the U.S., France, UK, Austria, and Germany. LOCATION:Berlin DTSTAMP:20251112T170935Z DTSTART:20160527T163000Z DTEND:20160527T180000Z END:VEVENT END:VCALENDAR