- Universität Zürich > Medizinische Fakultät > Neuropathologie, Institut für > Prof. Dr. Adriano Aguzzi
- Glatzel
Completed Research Project
- Title / Titel
- Role of the peripheral nervous system in prion neuroinvasion
- Summary / Zusammenfassung
- Prion diseases comprise a group of inevitably fatal neurodegenerative conditions affecting humans and animals. Due to distinctive neuropathological features, spongiform changes, and because of their infectious character, these diseases are also referred to as transmissible spongiform encephalopathies (TSEs). A wide body of data supports the idea that the causative agent responsible for these diseases consists principally or entirely of an abnormal isoform of a host encoded protein, the cellular prion protein; which is generally referred to as PrPSc.
For the most common human prion disease, sporadic Creutzfeldt-Jakob disease, the natural mode of transmission is unknown. In contrast, for other TSEs like bovine spongiform encephalopathy in cattle, scrapie in sheep, and iatrogenic or variant Creutzfeldt-Jakob (vCJD) disease of humans, the mode of transmission is thought to occur by peripheral uptake of infectious prions.
Prion Neuroinvasion:
One of the perplexing features of prion diseases is the long incubation time from peripheral uptake of prions until the onset of clinical symptoms. The incubation time can be, at least in part, attributed to the slow kinetics by which prions reach their target organ, the central nervous system (CNS). The process by which prions gain access to the CNS is generally referred to as neuroinvasion. The first phase involves the accumulation and possibly the propagation of prions in secondary lymphoid organs (LRS) such as lymph nodes, spleen or Peyer’s patches. The second phase of neuroinvasion comprises transport of infectious prions on or in peripheral nerves. Although this simplified two-phase model of neuroinvasion might not hold true in all instances and recent studies suggest that direct neuroinvasion along peripheral nerves occurs without the need for prion accumulation in secondary lymphoid organs, it is still the most accurate model to date.
In our research we are focusing on the role of the peripheral nerves in neuroinvasion.
We are pursuing three principle goals:
1) To determine the relevance of the cellular prion protein in neuroinvasion via peripheral nerves.
2) To precisely define types of peripheral nerves involved in prion neuroinvasion
3) To study modes of prion transport in peripheral nerves
- Publications / Publikationen
- Glatzel M, Aguzzi A. PrP(C) expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol. 2000;81:2813-2821Glatzel M, Aguzzi A. Peripheral pathogenesis of prion diseases. Microbes Infect. 2000;2:613-619Glatzel M, Heppner FL, Albers KM, Aguzzi A. Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron. 2001;31:25-34.
- Keywords / Suchbegriffe
- Prions, peripheral nerves, neurodegeneration, Creutzfeldt Jakob-Disease, sympathetic nervous system.
- Project Leadership and Contacts /
Projektleitung und Kontakte Dr. M. Glatzel (Project Leader) markus.glatzel@usz.ch Prof. A. Aguzzi adriano@pathol.uzh.ch
- Funding Source(s) /
Unterstützt durch - Forschungskredit der Universität Zürich, SNF (Personen- und Projektförderung), EU
- In Collaboration with /
In Zusammenarbeit mit Prof. U. Greber, Institute of Zoology, University Zürich Switzerland Prof. K.M. Albers, Neuroscience, University of Pittsburgh United States
- Duration of Project / Projektdauer
- Sep 2000 to Sep 2003