Prion diseases are a group of transmissible neurodegenerative disorders that include kuru, Creutzfeld-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals.

The diseases are characterized by cerebral accumulation of a misfolded, partially protease resistant form (PrP^Sc) of the cellular prion protein (PrP^C). This is followed by vacuolization of different areas in the brain which give rise to the name spongiform encephalopathies. The cause of the neurodegeneration and the vacuolization is not clear. We study factors that affect formation, clearance and spread of the prions in neural cell cultures. We have shown that lysosomal cysteine proteases, the cathepsins, are important for degradation of PrP^Sc in both neuronal cells and in immune cells. Factors that may be involved in the conversion of PrP^C into PrP^Sc are not yet known. We have shown that brain derived neurotrophic factor (BDNF) increases the amount of PrP^Sc in scrapie-infected neuronal cell lines, and that inhibition of one of the signaling pathways for BDNF inhibits formation of PrP^Sc. We also investigate other factors important for PrP^Sc formation.

There are evidences that prions are spread to the brain from the lymphoreticular system via nerve fibers innervating lymphatic organs (e.g. spleen). Mice lacking functional B-cells and follicular dendritic cells show resistance to prion infection and the role of different immune cells is under investigation. We have shown that bone marrow-derived dendritic cells can take up and degrade PrP^Sc. However how, and if, these cells play a role in prion spread is still unknown.  We have set up a cell culture system with neuronal cell-lines and primary cultures to investigate the role of the immune system in prion infection and uptake of prions to neurons.

The work on  prions is performed by:

Gia Luhr

Elin Nordström