NR AWHJ
AU Ishikawa,K.; Kudo,Y.; Nishida,N.; Iwaki,T.; Doh-ura,K.
TI Styrylbenzoazole derivatives for imaging of prion plaques and treatment of prion diseases
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions DIA-28
PT Konferenz-Poster
AB Recent prevalence of acquired forms of prion diseases has urged the development of early diagnostic measures as well as therapeutic interventions. We have previously reported that some amyloid imaging compounds, primarily derived from amyloid dyes such as Congo red and thioflavin T, are useful for detection of abnormal PrP plaques and treatment of prion diseases (Ishikawa et al., Journal of General Virology, 1785-90, 2004). To extend our previous findings on the utility of amyloid imaging probes toward a practical step, we have developed and analyzed styrylbenzoazole derivatives with more adequate permeability of blood brain barrier (BBB). The new styrylbenzoazole compounds clearly labeled abnormal PrP plaques in the human brain specimens in a manner irrespective of pathogen strain. A representative compound BF-168 detected abnormal PrP aggregates in the brain of experimental animals when BF-168 was injected intravenously. On the other hand, most of these styrylbenzoazole derivatives inhibited abnormal PrP formation in prion-infected cells with IC50 values in the nanomolar range, indicating one of the most potent classes of inhibitor ever reported. Additionally, BF-168 prolonged the lives of intracerebrally prion-infected mice when the compound was given intravenously at the preclinical stage. The new compounds, however, could not detect synaptic PrP deposition or show pathogen-independent therapeutic efficacy, similar to the amyloid imaging probes we previously reported. The compounds were efficiently BBB-permeable and nontoxic at doses for imaging and treatment in this study; therefore, they are expected as novel lead compounds of therapeutic drugs as well as imaging probes for prion diseases.
AD K. Ishikawa, K. Doh-ura: Department of Prion Research, Tohoku University Graduate School of Medicine, Sendai, Japan; Y. Kudo: Division of Telecommunication and Information Technology, Biomedical Engineering Research Organization, Tohoku University, Sendai, Japan; N. Nishida: Division of Cellular and Molecular Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; T. Iwaki: Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. E-mail: ishikawa@mail.tains.tohoku.ac.jp
SP englisch
PO Italien