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Spreading the Bad News: an Update on the Role of Pathological Proteins in Neurodegenerative Diseases XXX OTTORINO ROSSI AWARD New Series “The Pavia Legacy”

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Spreading the Bad News: an Update on the Role of Pathological Proteins in Neurodegenerative Diseases XXX OTTORINO ROSSI AWARD New Series “The Pavia Legacy” Scientific conference December 20th 2019 Spreading the bad news: an update on the role of pathological proteins in neurodegenerative diseases XXX OTTORINO ROSSI AWARD NeW SeRIeS “The PAvIA legAcy” IRCCS Mondino Foundation Pavia, via Mondino 2, Berlucchi Hall www.mondino.it Ottorino Rossi / Historical notes Ottorino Rossi was born on 17th January, was instrumental in getting the buildings origin. He died in 1936 at the age of 59, 1877, in Solbiate Comasco, near Como, of the new San Matteo General Hospital having named the Ghislieri College as his Italy. In 1895 he enrolled at the medical completed. heir. Ottorino Rossi was one of Camillo faculty of the University of Pavia as a Ottorino Rossi made many important Golgi’s most illustrious pupils as well as student of the Ghislieri College and during scientific contributions to the fields one of the most eminent descendants of his undergraduate years was an intern of neurology, neurophysiopathology Pavia’s medico-biological tradition. pupil of the Institute of General Pathology and neuroanatomy. These include: Since 1990, thanks to an initiative and Histology, headed by Camillo Golgi. In the identification of glucose as the launched by the Scientific Director at the 1901 Rossi obtained his medical doctor reducing agent of cerebrospinal fluid, time (Prof. Giuseppe Nappi), the IRCCS degree with the highest grades and a the demonstration that fibres from the Mondino Foundation has held an annual distinction. In October 1902 he went on to spinal ganglia pass into the dorsal branch conference at which an award dedicated the Clinica Neuropatologica (Hospital for of the spinal roots, and the description of to the memory of Ottorino Rossi is Nervous and Mental Diseases) directed the cerebellar symptom which he termed presented to a scientist who has made an by Casimiro Mondino to continue his “the primary asymmetries of positions”. important contribution to research in the studies. At the same time, he continued Moreover, he conducted important field of the neurosciences. to frequent the Golgi Institute which was studies on the immunopathology of Recent years have seen the introduction the leading Italian centre for biological the nervous system, the serodiagnosis of a new Ottorino Rossi Award series, research. Having completed his clinical of neurosyphilis and the regeneration aimed at rewarding eminent researchers preparation in Florence under Eugenio of the nervous system. He was the with cultural and scientific links with the Tanzi, and in Munich at the Institute author of major scientific works city of Pavia. Having been informally directed by Emil Kraepelin, he taught at including an extensive investigation started in 2017, on the occasion of the the Universities of Siena, Sassari and, of arteriosclerosis in the brain, centenary of the Mondino Foundation, from 1925, Pavia. In Pavia he was made L’Arteriosclerosi dei Centri Cerebrali this new series was officially inaugurated Rector of the University (serving from e Spinali (1906), which dealt with the in 2018, under the heading “The Pavia 1925 to 1936), and during his tenure he development of lesions of vascular legacy”. 2 Adriano Aguzzi / Ottorino Rossi Award 2019 Adriano Aguzzi was born in Pavia in in vivo model of microglia depletion, 1960. After graduating from high school, which helped to show the vigorous anti- he moved to the University of Freiburg, prion activity of microglia. Aguzzi’s work Germany, where he obtained his MD led to the identification of the cell types degree in 1986. Following postdoctoral and molecules that enable invasion of studies in Vienna, he received the the brain by prions, and highlighted venia legendi in neuropathology the role of follicular dendritic cells as at the University of Zurich in 1993, the “prion factories” in extracerebral where he is currently Full Professor tissues. He identified plasminogen as of Neuropathology, Director of the a prion carrier in blood, and improved Institute of Neuropathology and the process of differentiation of prion Chairman of the Interfaculty MD-PhD strains by fluorescence spectroscopy. Committee. Aguzzi’s lab also found that prion neuroinvasion and the mechanisms that Adriano Aguzzi has devoted his career protein of neuronal origin prevents cause brain damage in these conditions, to studying the immunological and demyelination, thus highlighting a while critically analyzing whether and molecular basis of human prion diseases, possible physiological role of this how such mechanisms may be shared a group of fatal neurodegenerative protein, and therefore the potential by neurodegenerative diseases more conditions characterized by neuronal existence of new therapeutic targets. frequent in the general population. loss, vacuolation and glial activation. Through his pioneering work, Adriano The Ottorino Rossi Award 2019 is He is both founder and Director of Aguzzi has made a highly original and therefore bestowed on Prof. Adriano the Swiss National Reference Center fundamental contribution to research Aguzzi in recognition of his relentless for Prion Diseases and has developed into prion diseases, and become a investigation into the most intimate diagnostic and therapeutic methods in towering figure in the field of modern mechanisms of neurodegeneration, and the field of transmissible spongiform neuroscience. His studies have revealed thus for his outstanding contribution to encephalopathies. He invented the first the cells and molecules involved in prion the advancement of neuroscience. 3 Previous Winners / Ottorino Rossi Award 1990 1998 2005 2013 Vittorio Erspamer Alain Berthoz Jes Olesen Henry Markram Rome (Italy) Paris (France) Copenhagen (Denmark) Lausanne (Switzerland) 1991 2006 1999 2014 Paolo Pinelli Stanley Finger Ottar Sjaastad Milan (Italy) S. Louis (USA) Emmanuele A. Jannini Trondheim (Norway) L’Aquila (Italy) 1992 2007 Giovanni Di Chiro 2000 Michael A. Moskowitz 2015 Bethesda (USA) John Timothy Boston (USA) Roberto Crea Greenamyre 1993 2008 Hayward (USA) Atlanta (USA) Clarence Joseph Gibbs Patricia Smith Churchland 2016 Bethesda (USA) San Diego (USA) 2001 Richard Stanislaus 1994 Salvatore Di Mauro 2009 Joseph Frackowiak David Zee New York (USA) Stephen P. Hunt Lausanne (Switzerland) Baltimore (USA) London (UK) 2002 2017 1995 2010 Elio Raviola Pierluigi Nicotera Elio Lugaresi Boston (USA) Vincenzo Bonavita Bologna (Italia) Naples (Italy) Bonn (Germany) 2003 1996 2011 2018 Michael Welch Michel Fardeau Cesare Fieschi Gianvito Martino Chicago (USA) Paris (France) Rome (Italy) Milan (Italy) 1997 2004 2012 Salvador Moncada François Boller Giorgio Bernardi London (UK) Paris (France) Rome (Italy) 4 5 Background to the conference This conference will address the and intracellular aggregation. By gression, to detect the presence role of pathological proteins in the sowing the pathology among still and topographical distribution of pathogenesis, pathophysiology unaffected neuronal populations, these proteins in the brain. and clinical evolution of major neu- they have the effect of “spread- The conference format will reflect rodegenerative diseases, such as ing the bad news” throughout the this conceptual framework. There Alzheimer’s disease, Parkinson’s areas of the central nervous system will be three lectures per topic disease and the clinical spectrum affected by the above-mentioned area, which will illustrate the state that includes amyotrophic lat- diseases. of the art with regard to pre-clin- eral sclerosis and frontotemporal Gaining a deeper insight into the ical research, clinical correlates dementia. This is currently a key intrinsic mechanisms governing and therapeutic implications, and area of research in the field of neu- these dynamics, and learning how advanced neuroimaging. rodegeneration, sparked, in recent the spread of pathological pro- years, also by the groundbreaking teins can affect the clinical mani- work on the molecular basis and festations and evolution of these cell biology of prion diseases done diseases, is central to the devel- by the winner of the 30th Ottorino opment of innovative therapeutic Rossi Award. strategies targeting these proteins. Distinct proteins — such as Equally crucial is the availability of b-amyloid, tau, a-synuclein and reliable neuroimaging techniques TDP-43 — may follow similar able, for diagnostic purposes and patterns of cell-to-cell transfer for the monitoring of disease pro- 6 Programme 8.45 Registration and welcome coffee CONFERENCE spreading the bad news: an update 9.30 Greetings from the Authorities on the role of pathological proteins in neurodegenerative diseases XXX OTTORINO ROSSI AWARD CEREMONY ALZHEIMER’S DISEASE Chairpersons: Stefano Cappa (Pavia) 9.45 Presentation of the Winner Fabrizio Tagliavini (Milan) Lecture by the Winner 11.00 Oligomers: disease spreading and toxicity 10.00 The peculiar, fascinating biology Gianluigi Forloni (Milan) of mammalian prions Adriano Aguzzi (Zurich) 11.35 Clinical relevance of neuropathological changes in Alzheimer’s disease Alessandro Padovani (Brescia) 12.10 Tau, Ab and network degeneration in Alzheimer’s disease Rik Ossenkoppele (Amsterdam) 12.45 Lunch 7 Programme PARKINSON’S DISEASE 15.30 Mechanism of aggregation, seeding Chairpersons: Fabio Blandini (Pavia) and toxicity in ALS and FTD Antonio Pisani (Rome) Magdalini Polymenidou (Zurich) 13.45 Alpha-Synuclein: a troublesome traveller 16.05 The clinical relevance of contact- Donato A. Di Monte (Bonn) dependent/independent cell-to-cell trasfer of TDP-43 and SOD1 in ALS/FTD 14.20 Clinical evolution in Parkinson's
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