Amyloid imaging probes are useful for detection of prion plaques and treatment of transmissible spongiform encephalopathies

Kensuke Ishikawa, Katsumi Doh-ura, Yukitsuka Kudo, Noriyuki Nishida, Ikuko Murakami-Kubo, Yukio Ando, Tohru Sawada, Toru Iwaki

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders. A thioflavin derivative, 2-[4′-(methylamino)phenyl] benzothiazole (BTA-1) and a Congo red derivative, (trans, trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) are representative chemicals of these probes. In this report, the two chemicals were studied in transmissible spongiform encephalopathies (TSE). Both BTA-1 and BSB selectively bound to compact plaques of prion protein (PrP), not only in the brain specimens of certain types of human TSE, but also in the brains of TSE-infected mice when the probes were injected intravenously. The chemicals bound to plaques in the brains were stable and could be detected for more than 42 h post-injection. In addition, the chemicals inhibited abnormal PrP formation in a cellular model of TSE with IC50 values of 4 nM for BTA-1 and 1.4 μM for BSB. In an experimental mouse model, the intravenous injection of 1 mg BSB prolonged the incubation period by 14%. This efficacy was only observed against the RML strain and not the other strains examined. These observations suggest that these chemicals bind directly to PrP aggregates and inhibit new formation of abnormal PrP in a strain-dependent manner. Both BTA-1 and BSB can be expected to be lead chemicals not only for imaging probes but also for therapeutic drugs for TSEs caused by certain strains.

Original languageEnglish
Pages (from-to)1785-1790
Number of pages6
JournalJournal of General Virology
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 1 2004

All Science Journal Classification (ASJC) codes

  • Virology

Fingerprint Dive into the research topics of 'Amyloid imaging probes are useful for detection of prion plaques and treatment of transmissible spongiform encephalopathies'. Together they form a unique fingerprint.

  • Cite this