Structure-activity analysis and antiprion mechanism of isoprenoid compounds

Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Kenta Teruya, Katsumi Doh-ura

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The prion strain-specific mechanism by which normal prion protein is converted to abnormal prion protein remains largely unknown. This study found that insect juvenile hormone III reduced abnormal prion protein levels only in cells infected with the RML prion. We conducted a structure-activity analysis using juvenile hormone III biosynthetic intermediates in the isoprenoid pathway. Both farnesol and geranylgeraniol, the most potent inhibitors of abnormal prion protein formation, behaved in an RML prion-dependent fashion. Neither of them modified cellular and cell surface prion protein levels. Events downstream of this pathway include cholesterol biosynthesis and protein prenylation. However, neither of these isoprenoid compounds modified lipid raft microdomains and cellular cholesterol levels and neither affected the representative prenylated protein expression levels of prenylation pathways. Therefore, these isoprenoid compounds are a new class of prion strain-dependent antiprion compounds. They are useful for exploring strain-specific prion biology.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalVirology
Volume486
DOIs
Publication statusPublished - 2015 Dec 1

Keywords

  • Antiprion
  • Cholesterol
  • Farnesol
  • Geranylgeraniol
  • Isoprenoid
  • Juvenile hormone
  • N2a cell
  • Prenylation
  • Prion
  • Strain

ASJC Scopus subject areas

  • Virology

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