NR ATQU
AU Bera,A.; Nandi,P.K.
TI Biological amines prevent nucleic acid catalysed prion protein polymerizaton to amyloid
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-10
PT Konferenz-Poster
AB We previously showed that nucleic acid can catalyse the conversion of recombinant prion protein to prion protein oligomers and amyloid polymers of different morphologies including spheroamyloids similar to the structures observed in prion infected animal and human brains. Results from other laboratories also suggest that nucleic acid can be a cofactor for the conversion of the prion protein to its infectious form. Studies in the literature show the presence of prion protein in the cell cytoplasm. However, nucleic acids exist as complexes with polyamines [spermine NH2(CH2)3NH-(CH2)4 NH (CH2)3NH2 and spermidine (H2N(CH2)3NH(CH2)4NH2) which are present in milimolar concentrations] in the cytoplasm of cells including brain cells. These amines are positively charged at physiologically relevant ionic and pH conditions and can cross the blood brain barrier. We here present the solution results to show that increasing concentrations of spermine and spermidine reduce nucleic acid (tRNA and double stranded) catalysed polymerisation of prion protein and at their physiological concentrations these amines prevent the polymerisation of the protein by nucleic acid. We find that these amines also reduce the extent and prevent nucleic acid induced unfolding of the structured C-terminal segment of the prion protein which unlike full length positively charged protein has a pK value around neutral pH. In the above experiments, spermine is found to be more effective than spermidine in influenncing the nucleic acid effect on prion protein. Although no comparative data of the level of these polyamines for prion infected subjects with control are available, in Alzheimer disease the levels of these amines have been found to decrease considerably. A correlation of the levels of the polyamines with the prion disease is necessary for exploration of their roles in preventing the disease if nucleic acid plays a role of cofactor in the prion disease.
AD A.Bera, P.K.Nandi, Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique
SP englisch
PO Deutschland