BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Mechanism of alpha-synuclein toxicity in Parkinson's disease. - Pr ofessor Maria Grazia Spillantini\, Department of Clinical Neurosciences\, Cambridge DTSTART:20090929T100000Z DTEND:20090929T103000Z UID:TALK18685@talks.cam.ac.uk CONTACT:Hannah Critchlow DESCRIPTION:This talk is part of the Cambridge Clinical Neuroscience and M ental Health Symposium\, 29th - 30th September 2009 at West Road Concert H all. This event is free to attend for cambridge neuroscientists although r egistration is required. To register\, and for further information\, pleas e visit: http://www.neuroscience.cam.ac.uk/cnmhs/\n\nAbstract: Parkinson's disease (PD) is the most common movement disorder clinically characterize d by rigidity\, resting tremor and bradikenisia which are associated with degeneration of neurones in the substantia nigra. Neuropathologically PD i s characterized by the presence of intracellular filamentous protein aggre gates known as Lewy bodies. Genetic mutations and multiplications of the a lpha-synuclein gene cause familial forms of PD and alpha-synuclein has bee n shown to be the major component of the Lewy bodies (1). These findings c learly associate the pre-synaptic protein alpha-synuclein to PD pathogenes is although\, its toxic function remain unclear as unclear is whether prot easome dysfunction and oxidative stress are a cause or consequence of alph a-synuclein accumulation. We have produced a transgenic mouse that express es truncated 1-120 human alpha-synuclein under the control of the tyrosine hydroxylase promoter. In these mice truncated alpha-synuclein aggregates into granular and filamentous material and this aggregation is associated with dopamine loss and appearance of motor impairment in the absence of do paminergic cell death (2). In these mice we do not find alterations in pro teasome and aconitase activities or authophagy while an altered synaptic d istribution of alpha-synuclein is present. This result suggests that PD co uld start at the synapse. \n\nReferences:\n1- Tofaris GK\, Spillantini MG. Physiological and pathological properties of alpha-synuclein. Cell Mol L ife Sci. 64\, 2194-201\, 2007\n\n2-Tofaris GK\, Garcia Reitböck P.\, O’ Connell M.\, Ghetti B.\, Humby T.\, Lambourne L.\, Gossage H.\, Emson P.C. \, Wilkinson L.S.\, Goedert M.\, Spillantini M.G.: Pathological changes in dopaminergic neurones in mice transgenic for human -synuclein (1-120): implications for Lewy body disorders. J Neurosci 26\, 3942-3950\, 2006.\n \nBiosketch: Maria Grazia Spillantini is Professor of Molecular Neurology at the Clinical School of the University of Cambridge\, UK. She was born i n Arezzo\, Italy. After receiving a Laurea in Biological Sciences\, summa cum Laude\, in 1981 from the University of Florence\, Italy\, she pursued research at the Department of Clinical Pharmacology of the University of F lorence\, at the Unit's de Neurobiologie of the INSERM in Paris and at the Molecular Neurobiology Unit of the Medical Research Council in Cambridge. In 1987 she moved to the Medical Research Council Laboratory of Molecular Biology\, where first\, working in Dr Michel Goedert's group\, she obtain ed a Ph.D. in Molecular Biology from Cambridge University (Peterhouse) and later she worked as postdoctoral fellow with Prof. Sir Aaron Klug. In 199 6 she moved to the Brain Repair Centre of the University of Cambridge at t he Department of Clinical Neurosciences where she is at present. Her group works on the molecular neuropathology of diseases characterised by tau an d alpha-synuclein aggregates. She identified alpha-synuclein as the major component of the Lewy bodies in Parkinson's disease and dementia with Lewy bodies and described one of the first mutations in the Tau gene leading t o Frontotemporal dementia and Parkinsonism linked to chromosome 17. She i s an official fellow of Clare Hall and life member of Peterhouse LOCATION:West Road Concert Hall END:VEVENT END:VCALENDAR