A new study has shed light on the cellular and molecular mechanisms underlying the progression of prion diseases, like Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, and has identified a potential target for treatment. The research is described in a paper published yesterday in PLOS Pathogens.
Researchers from Boston University School of Medicine used a method they previously described for culturing nerve cells from the hippocampal region of the brain, and then exposing them to prions, to illustrate the damage to nerve cell connections usually seen in these diseases. They then added a number of different chemical compounds with known inhibitory effects on cellular responses to stressful stimuli, with the objective of identifying which pathways may be involved.
They found that inhibition of p38 MAPKα (an enzyme that typically responds to stress, such as ultraviolet radiation and heat shock) prevented injury to nerve connections and promoted recovery from the initial damage. Hippocampal nerve cells that had a mutation preventing normal function of p38 MAPKα were also protected, seeming to confirm the role the enzyme plays in this disease process.
David. A. Harris, M.D., Ph.D., professor and chair of the department of biochemistry and corresponding author of the study, sees these findings as a major breakthrough in trying to understand and treat these diseases. "Our results provide new insights into the pathogenesis of prion diseases, they uncover new drug targets for treating these diseases, and they allow us to compare prion diseases to other, more common neurodegenerative disorders like Alzheimer's disease."