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.