The process by which a normal prion protein (provoked by an abnormal prion) undergoes a conformational change to the abnormal form, and the hypothesized resulting neuropathology, is of particular interest to researchers of other neurodegenerative diseases that also feature abnormal buildup of toxic proteins. Because the presence of abnormal prion alone does not lead to neurodegeneration, it is assumed that the protein must work via other molecules. Adriano Aguzzi and colleagues in Switzerland and Austria determined that plasminogen-a plasma component that serves as the proenzyme for the protease plasmin-binds selectively to the prion protein in its abnormal form, probably via lysine residues on the prion. They found this to be true with mouse prion protein, as well as with prion protein from the brains of human Creutzfeldt-Jakob disease patients.

"Plasminogen represents the first endogenous factor discriminating between normal and pathological prion protein," write the authors. An obvious line of research is now to determine if there could be any pathological consequences to this binding. (To that end, e.g., plasminogen has been shown to play a role in neuronal death in the hippocampus, and normal plasmin proteolysis is important in synaptic remodeling and LTP.) On another front, the authors suggest that plasminogen might be the basis of a test to identify the presence of the abnormal protein-or even technologies to reduce the abnormal protein load.-Hakon Heimer.

Reference:Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A. Binding of disease-associated prion protein to plasminogen. Nature 2000 Nov 23;408(6811):479-83. Abstract