Aguzzi
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Aguzzi
Completed research project
| Title / Titel | Understanding peripheral prion pathogenesis | ||
|---|---|---|---|
| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy (BSE), variant Creutzfeldt-Jakob disease (vCJD), kuru, and most cases of iatrogenic CJD. The applicant has studied cell populations and molecules involved in neuroinvasion – the process by which prions colonize the central nervous system (CNS) upon peripheral infection. Here we propose a triennial research program addressing questions that have emerged from our previous studies. We will dissect pathogenesis of prion diseases by combining transgenetics, cellular and molecular immunology, and advanced imaging tech-niques. The present proposal is articulated/encompasses the following specific aims: 1. Prion pathogenesis and the immune system. a. Role of granulomatous inflammation in prion pathogenesis. b. Inflammatory kidney conditions and prion pathogenesis. c. Lymphotoxin: a prion pathogenesis switch? d. Trogocytosis and transcellular prion transfer. e. Function of PrPC in lymphocyte homeostasis. f. Differential lymphotropism of prion strains. 2. A search for peripheral prion receptors. a. Role of Toll-like receptors in prion pathogenesis. b. CD21: a peripheral prion receptor? 3. Post-lymphatic peripheral prion pathogenesis. a. Axonal transport in prion pathogenesis. b. Prion transmission by aerosols. c. Assessment of the contribution of microglia to scrapie pathogenesis. 4. Prion diagnostics in extraneural compartments. a. Monoclonal antibodies to discriminatory PrP epitopes. b. Identifying prion-infected cells with rationally designed immunoreagents. In view of the possibility that neuroinvasion of BSE prions may elicit an epidemic in humans, particular emphasis will be put on the translational fallout of our research, i.e. its relevance to developing sensitive diagnostics and post-exposure prophylaxis against prion infections. |
||
| Keywords / Suchbegriffe | prions, scrapie, strains, follicular dendritic cells, inflammation, lymphotoxin, microglia, biosafety, aerosols, prionuria, diagnostics, post-exposure prophylaxis | ||
| Project leadership and contacts / Projektleitung und Kontakte |
|
||
| Other links to external web pages | http://www.neuropathologie.usz.ch/ | ||
| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
||
| Duration of Project / Projektdauer | Jun 2006 to May 2009 |