Plasminogen Stimulates Formation of Pathogenic Prion Clumps

Compared to control PMCA conducted without plasminogen, addition of plasminogen in PMCA using wild-type brain material significantly increased PrP conversion. PrP conversion in PMCA was substantially less efficient with plasminogen-deficient brain material than with wild-type material.
Stimulation of PrP conversion was specific for plasminogen and depended on plasminogen's kringle domains. This activity was eliminated by modification of plasminogen structure or interference with the PrP-plasminogen interaction. When added to cell cultures, plasminogen and kringles were found to promote PrP propagation in ScN2a and Elk 21+ cells.

"I hope that our study will aid in developing therapy for prion diseases, which will ultimately improve the quality of life of patients suffering from prion diseases," said senior author Dr. Chonsuk Ryou, professor of microbiology, immunology, and molecular genetics at the University of Kentucky. "Since prion diseases can lay undetected for decades, delaying the ability of the disease-associated prion protein to replicate by targeting the cofactor of the process could be a monumental implication for treatment."

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