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Florida Faculty and Professional Staff

Corinne Lasmezas

Education 

Research Focus 

Prion diseases are fatal neurodegenerative diseases affecting humans and animals. They are caused by an unconventional infectious agent called prion, which is thought to be composed mainly by a misfolded form of a host protein, the prion protein (PrP). In humans, the condition called Creutzfeldt-Jakob disease is very rare (one case per million inhabitants per year throughout the world), but in animals scrapie has been known to ravage flocks for two hundred years. The recent epidemic of bovine spongiform encephalopathy in the United Kingdom (with more than 180 000 affected cows in this country) has caused major turmoil throughout Europe, and even later, in other countries such as Japan, Canada and the United States. Indeed, the latter, as opposed to sheep scrapie, is transmissible to humans and 184 human lifes have been lost as of August 2005. In addition, the beef industry had to face major economical losses due to the reduction in the consumption of beef products and the implementation of measures to protect the human food chain.

Recent years have witnessed a wealth of data showing the implication of the prion protein in disease susceptibility and its contribution to the replication of the prion. However, there are still major areas which need to be deciphered, amongst which : how does the prion enter into a cell and spread to another one ? Which host factors does it bind to in order to enable its multiplication ? What exactly causes the death of the neurons ? What would be the best approach to impede prion replication ? Block the protein itself or interfere with a ligand ? Is there a way to prevent neuronal death ?

Much of our past effort has been dedicated to understand the pathogenesis and the mechanisms of prion transmission from one species to another and its propagation within the body. We also studied the neurotoxic mechanisms and showed, using primary cultures of neurons, that low molecular weight aggregates of the prion protein are neurotoxic. In collaborative studies, we have found that the non integrin laminin receptor can act as a cellular receptor for the prion protein. Our aim now is to devise intervention strategies based on the blockage of the neurotoxic entities on the one hand, and of prion replication on the other hand, using a two step approach in scrapie-infected cells and rodent models of prion diseases.

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