Adriano Aguzzi

Adriano Aguzzi (born December 1, 1960 in Pavia , Italy ) is an Italian-Swiss physician and professor at the University of Zurich .

Life

Aguzzi studied medicine from 1980 to 1986 at the Albert Ludwigs University of Freiburg and the University of Basel , where he was also on a research stay at Columbia University . He dealt with neuro-oncology and neurovirology and developed a technique for inducing brain tumors by gene transfer into the telencephalon tissue. He later also applied the methods he developed in prion research. After receiving his doctorate in Freiburg, he worked as a neuropathologist at the University Hospital Zurich . In 1989 he moved to the Research Institute for Molecular Pathology (IMP) of the pharmaceutical company Boehringer Ingelheim in Vienna with Erwin Wagner , which he left in 1992 to return to Zurich a year later as a senior physician and private lecturer. There he worked with Charles Weissmann . In 1993 he completed his habilitation and became a private lecturer in neuropathology. His habilitation thesis in 1996 dealt with transgenic models of neuro carcinogenesis and neurodegenerative diseases . Since the end of 1995 he has been director of the Swiss “National Reference Center for Prion Diseases ” (NRPE), which is the focus of his research. In 1997 he was appointed director and professor of the "Institute for Neuropathology" at the University of Zurich.

plant

With his basic research , Aguzzi was able to provide evidence of the role the immune system plays in the spread of pathologically altered proteins , so-called prions , and thus reveal new therapeutic options. In 1993 he and Weissmann showed that the Prnp gene (PrPC is the normal prion protein that is defective in the disease, Prnp the associated gene) is necessary for the reproduction of prions, and he showed in a much-cited paper in Nature from 1996 that PrPC gene expression is necessary for the onset of the disease (by planting a gene for overexpression of (normal) PrPC from transgenic mice in the brain of Prnp knockout mice ). Then he dealt with the question of how prions get into the brain. In 1997 he found that this required non-blood cells with PrPC gene expression. According to Aguzzi, the infection takes place in several steps, first overcoming the epithelial cells , then the lymph nodes and finally via the peripheral nerves into the central nervous system. His laboratory also developed diagnostic methods for prions (in 2000 his group first identified plasminogen as a component of blood plasma that binds to PrPC) and possible therapeutics: in 2003 they found that the soluble dimer of the prion protein couples to the defective prion protein PrPs and another Prevents infection (it cannot be converted to the faulty variant of the protein). In 2007 he developed a diagnostic method for prion strains based on fluorescence spectroscopy. When investigating the role of the immune system in 1997, he and his group showed that B cells are necessary for the spread of the infection via their presentation of lymphotoxin ( tumor necrosis factor C) for the follicular dendritic cells (FDC). If this signaling path is shut down, the number of prions in the lymphatic system is reduced and soluble lymphotoxin receptors have proven to be a possible way of prophylaxis against prions after infection. The positioning of the FDC determined the spread of the infection in the nervous system. His group also showed that the uptake of prions at FDC is mediated by the complement system and that antibodies against the disease can be effective with the possibility of vaccine development. ${\displaystyle \beta }$ ${\displaystyle \beta }$

In this context, he examined the progenitor cells of FDC and found that they often occurred in the perivascular space . His group also investigated the pathogenic mechanisms of prions in brain cells and developed an ex vivo model (POSCA, for prion organotypic slice culture assay ) with which the activity of microglial cells against prions could also be studied, and they are investigating the function of the healthy prion protein PrPC.

In the epidemiology of Creutzfeldt-Jakob disease (CJD), he found an unexplained increase in Switzerland in 2002 and an accumulation of defective prion proteins in the spleen and skeletal muscles (with effects on necessary protective measures). He also found connections between the spread of prion diseases and (chronic) inflammation (e.g. increased excretion of prions via secretions and excretions in sheep and mice in the event of inflammation).

Awards and memberships

For his pioneering research achievements, Aguzzi received the Cloëtta Prize in 1998 , the Robert Koch Prize in 2003 , the Antonio Feltrinelli Prize in 2009 and, together with Charles Weissmann, the Hartwig Piepenbrock-DZNE Prize in 2013 . In 2017 he was awarded the InBev-Baillet Latour Health Prize .

Aguzzi is a corresponding member of the Austrian Academy of Sciences . In 2001 he was elected a member of the Leopoldina . He is an honorary doctor of the University of Teramo, the University of Liège. From 1998 to 2002 he was President of the Swiss Society for Neuropathology. In 1998 he became a member of EMBO . In 1996 he became a Fellow of the Royal College of Pathologists and in 2000 of the Royal College of Physicians (2002 Fellow). In 2011 he was elected a Fellow of the American Association for the Advancement of Science .

Fonts (selection)

• Effect of genetically engineered interferons on melanoma cells in vitro. Biosynthesis, expression and release of tumor-associated antigens and histocompatibility antigens , dissertation Freiburg im Breisgau 1986
• Transgenic models of neurocarcinogenesis and of neurodegenerative disorders . Zurich 1996. Habilitation, Univ. Zurich, 1996.
• Detlev Ganten (Ed.) With contributions by Adriano Aguzzi et al .: Diseases of the central nervous system . Springer, Berlin 1999. 575 S. Series: Handbuch der Molekularen Medizin Vol. 5; ISBN 3-540-64552-7
• Ernst-Ludwig Winnacker (Ed.): Under every stone lies a diamond: structure - dynamics - evolution . Hirzel, Stuttgart 2001. With contributions by Adriano Aguzzi et al. (Negotiations of the Society of German Natural Scientists and Doctors, footnote 121st Assembly, September 16-19, 2000, Bonn) ISBN 3-7776-1122-0
• with H. Büeller, C. Weissmann a. a .: Mice devoid of PrP are resistant to scrapie , Cell, Volume 73, 1993, pp. 1339-1347, PMID 8100741
• with S. Brandner, C. Weissmann u. a .: Normal host prion protein necessary for scrapie-induced neurotoxicity , Nature, Volume 379, 1996, pp. 339-343.
• with T. Blättler u. a .: PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain , Nature, Volume 389, 1997, pp. 69-73.
• with C Weissmann: Prion research: the next frontiers , Nature, Volume 389, 1997, pp. 795-798.
• with MA Klein u. a .: A crucial role for B cells in neuroinvasive scrapie , Nature, Volume 390, 1997, pp. 687-690.
• with C. Weissmann: Perspectives: neurobiology. PrP's double causes trouble , Science, Volume 286, 1999, pp. 914-915.
• with MB Fischer u. a .: Binding of disease-associated prion protein to plasminogen , Nature, Volume 408, 2000, pp. 479-483.
• with MA Klein u. a .: Complement facilitates early prion pathogenesis , Nature Medicine, Volume 7, 2001, pp. 488-492.
• with FL Heppner u. a .: Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies , Science, Volume 294, 2001, pp. 178-182.
• with S. Brandner u. a .: Spongiform encephalopathies: insights from transgenic models , Advances in Virus Research, Volume 56, 2001, pp. 313-352.
• with M. Glatzel u. a .: Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion , Neuron, Volume 31, 2001, pp. 25-34.
• with M. Glatzel u. a .: Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease , New England J Medicine, Volume 349, 2003, pp. 1812-1820.
• with P. Meier u. a .: Soluble dimeric prion protein binds PrP (Sc) in vivo and antagonizes prion disease , Cell, Volume 113, 2003, pp 49-60.
• with M. Prinz u. a .: Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion , Nature, Volume 425, 2003, pp. 957-962.
• with M. Heikenwalder: Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration , Nature Medicine, Volume 10, 2004, pp. 187-192.
• with FL Heppner u. a .: Experiment al autoimmune encephalomyelitis repressed by microglial paralysis , Nature Medicine, Volume 11, 2005, pp. 146-152.
• with M. Heikenwalder u. a .: Chronic lymphocytic inflammation specifies the organ tropism of prions , Science, Volume 307, 2005, pp. 1107-1110.
• with H. Seeger u. a .: Coincident scrapie infection and nephritis lead to urinary prion excretion , Science, Volume 310, 2005, pp. 324-326
• with M. Heikenwalder u. a .: Lymphotoxin-dependent prion replication in inflammatory stromal cells of granulomas , Immunity, Volume 29, 2008, pp. 998-1008.
• with J. Falsig u. a .: A versatile prion replication assay in organotypic brain slices , Nature Neuroscience, Volume 11, 2008, pp. 109-117
• with NJ Krautler u. a .: Follicular dendritic cells emerge from ubiquitous perivascular precursors , Cell, Volume 150, 2012, pp. 194-206.
• with J. Falsig: Prion propagation, toxicity and degradation , Nature Neuroscience, Volume 15, 2012, pp. 936-939
• with T. Sonati a. a .: The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein , Nature, July 31, 2013

Web links

• Website at the University of Zurich
• Literature by and about Adriano Aguzzi in the catalog of the German National Library
• Interview with Aguzzi in der Welt on March 14, 2001

Individual evidence

1. ^ Slz: Robert Koch Prize awarded to Adriano Aguzzi. In: Neue Zürcher Zeitung . October 28, 2003, accessed May 18, 2018 . 
2. ↑ 50,000 euros for Professor Adriano Aguzzi. (PDF; 103 kB) University of Zurich, September 11, 2013, accessed on May 18, 2018 . 
3. ↑ Member entry by Prof. Dr. Adriano Aguzzi (with picture and CV) at the Deutsche Akademie der Naturforscher Leopoldina , accessed on May 21, 2016.
4. ^ Fellows of the AAAS: Adriano Aguzzi. (No longer available online.) American Association for the Advancement of Science, archived from the original on January 22, 2018 ; accessed on January 22, 2018 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.