Role of lipid in forming an infectious prion?

The infectious agent of the transmissible spongiform encephalopathies, or prion diseases, has been the center of intense debate for decades. Years of studies have provided overwhelming evidence to support the prion hypothesis that posits a protein conformal infectious agent is responsible for the transmissibility of the disease. The recent studies that generate prion infectivity with purified bacterially expressed recombinant prion protein not only provides convincing evidence supporting the core of the prion hypothesis, that a pathogenic conformer of host prion protein is able to seed the conversion of its normal counterpart to the likeness of itself resulting in the replication of the pathogenic conformer and occurrence of disease, they also indicate the importance of cofactors, particularly lipid or lipid-like molecules, in forming the protein conformation-based infectious agent. This article reviews the literature regarding the chemical nature of the infectious agent and the potential contribution from lipid molecules to prion infectivity, and discusses the important remaining questions in this research area.