Scrapie, a naturally occurring disease of sheep and goats, produce a progressive degeneration of the central nervous system after a long incubation period. The disease is a prototype for the subacute spongiform encephalopathies, a group which includes three human disorders, Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome and kuru. Despite intense research efforts, the cause of mitochondria, mitoplasts and submitochondrial particles from scrapie-infected hamster brains are highly infectious. In addition, highly infectious prion protein enriched preparations (prion and SAF) contain mitochondrial nucleic acids. The mitochondrial nucleic acids present in these samples are enriched for a specific component of the mito-chondrial genome, the single-stranded displacement loop (D-loop) fragment. An abnormal D-loop fragment could affect both the replicative and transcription function of the mitochondria making basis for scrapie infectivity is compatible with many of the seeming disparate properties of the agent, including size and lack of immune response. This project is designed to search for nucleic acid differences between scrapie-infected and uninfected brain mitochondrial preparations. Strong emphasis is being placed on the characterization of nucleic acids contained within the mitochondria, specifically the D-loop fragment. In addition, infectivity studies will be performed on different mitochondrial fractions in an attempt to identify isolation procedures producing high titer scrapie samples. Our data indicates that scrapie is not a """"""""prion disease"""""""" and thus may be related to human neurological disorders such as Alzheimer's disease and Parkinsonism as well as being a model for aging.
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