Amyloid-binding compounds and their anti-prion potency.
Prion diseases, or transmissible spongiform encephalopathies, are characterized by abnormal prion protein accumulation in the brain. Abnormal prion proteins, having properties of amyloids when extracted from the brain, are observed as amyloid plaque deposits in the brain in some prion diseases such as variant Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome. This article reviews amyloid-binding compounds from the perspective of their usefulness for diagnosis and therapy of prion diseases. Styrylbenzoazole derivatives and phenylhydrazine derivatives are recently developed amyloid binding compounds that present benefits for prion-disease-related medicinal applications. For instance, styrylbenzoazole derivative BF-227, currently used as an amyloid imaging probe of positron emission tomography in Alzheimer disease, is useful also for the diagnosis of Gerstmann-Sträussler-Scheinker syndrome. A phenylhydrazine derivative, compB, has remarkable prophylactic effects on intracerebrally infected animals with certain prion strains, even when administered orally. These amyloid-binding compounds, however, are not applicable to prion strains or prion diseases of all types. For example, amyloid-binding compounds are ineffective for inhibiting prion strains such as 263K. They are not feasible for detecting abnormal prion protein accumulation in the brain for prion diseases having no amyloid plaques. To elucidate the limitations of amyloid-binding compounds, further investigation is necessary to clarify the binding mode of the compounds to abnormal prion protein structures at an atomic level.
Department of Neurochemistry, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan. doh-ura@med.tohoku.ac.jp.
Kenta
K
Teruya
Katsumi
K
Doh-ura
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010659:Phenylhydrazines / Q000737:chemistry / Q000494:pharmacology*; D017096:Prion Diseases / Q000188:drug therapy*; D011328:Prions / Q000037:antagonists & inhibitors*; D013844:Thiazoles
C516779:2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole; D000682:Amyloid; D001583:Benzoxazoles; D010659:Phenylhydrazines; D011328:Prions; D013844:Thiazoles; C030299:phenylhydrazine