Basic Medicine, Molecular and Cellular Biology, Neuroscience

Neurological Science

To Understand the Molecular Mechanisms of Prion Protein Conversion

Medical Sciences Course

  • Master / Doctoral Degree


KITAMOTO, TetsuyukiKITAMOTO, Tetsuyuki
KITAMOTO, Tetsuyuki

Professor, M.D. Ph.D.

*Concurrent Position

Research Theme

  • New diagnostic method to identify the acquired prion disease
  • Conversion-accelerating or ?inhibitory mechanism of prion protein
  • PrP polymorphism analysis in prion diseases
Research Keywords:

prion protein, normal polymorphism and mutations, conversion, transmission experiment, prion disease

Technical Keywords:

histopathological analysis, humanized knock-in mouse, western blot analysis, protein misfolding cyclic amplification, transmission experiments

Laboratory Introduction

We investigated prion diseases as a collaborating center of WHO (World Health Organization) since 1998 because of vCJD emerging infection from 1996, also as a center for analyzing the PRNP gene and evaluating the histopathology of Japanese CJD surveillance.
The recent achievements are as follows, the identification of the original prions (VV2 or MV2 prions) in dura-grafted CJD with kuru plaques(2), the highly sensitive detection method to amplify vCJD prions from the plasma, and the structural model of abnormal prion protein (5).
The future goals of our laboratory is to reveal the conversion mechanism of prion protein. By elucidation of this mechanism, we can achieve to the treatment or the prevention of the prion diseases.

Figure 1. Transmission experiment with humanized PrP knock-in mouse

Figure 1. Transmission experiment with humanized PrP knock-in mouse

Figure 2. Structural model of abnormal prion protein

Figure 2. Structural model of abnormal prion protein

Recent Publications

  • Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt-Jakob disease in cell-protein misfolding cyclic amplification. Takeuchi A, Kobayashi A, Parchi P, Yamada M, Morita M, Uno S, Kitamoto T. Lab Invest. 2016 May;96(5):581-7. doi: 10.1038/labinvest.2016.27. Epub 2016 Feb 15.
  • The influence of PRNP polymorphisms on human prion disease susceptibility: an update. Kobayashi A, Teruya K, Matsuura Y, Shirai T, Nakamura Y, Yamada M, Mizusawa H, Mohri S, Kitamoto T. Acta Neuropathol. 2015 Aug;130(2):159-70. doi: 10.1007/s00401-015-1447-7. Epub 2015 May 29. Review.
  • Takeuchi A, et al. Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes. J Biol Chem. 288:21659-21666, 2013.
  • Kobayashi A, et al. Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein. Acta Neuropathol Commun. 1:74(1-11), 2013.
  • Shirai T, et al. Evaluating prion models on comprehensive mutation data of mouse PrP Structure 22; 560-571, 2014.
  • Kobayashi A. et al. Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?. J Virol. 89(7):3939-46,2015.