Basic Medicine, Molecular and Cellular Biology, Neuroscience

Neurochemistry

To Challenge Intractable Diseases Caused by Mysterious Misfolded Proteins: Discovery of Remedies for Prion Disease, Prion-like Diseases and Amyloidoses

Medical Sciences Course

  • Master / Doctoral Degree

Faculty

DOH-URA, KatsumiDOH-URA, Katsumi
DOH-URA, Katsumi

Professor, M.D. Ph.D.

*Concurrent Position

Research Theme

  • Development of preventive and therapeutic methods, and search for novel drug targets and novel surrogate markers for prion disease
  • Elucidation of molecular mechanism of prion formation, by means of chemical biology and molecular biology
  • Development of preventive and therapeutic methods applicable to all prion-like diseases and amyloidoses
Research Keywords:

prion, misfolded protein, drug discovery, neuronal cell death, amyloidosis

Technical Keywords:

cell culture, animal experiment, chemical biology, molecular biology, pathology

Laboratory Introduction

Our research interests are basic science and applied medical science related to the diseases caused by misfolded protein accumulation in the brain or other organs, including prion disease, prion-like diseases (Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases) and amyloidoses. All these incurable diseases appear age-dependently in a sporadic manner in some cases and in a hereditary manner in other cases, and the pathological processes of the diseases are proposed to share similar molecular degenerative pathways in the brain or organs, which are not fully elucidated. The nature of misfolded proteins, especially prion, is still one of the most challenging enigmas in science, because misfolded proteins which are free of genomes transmit the pathological conditions into normal cells, and even into healthy individuals. Actually, recent outbreaks of new types of prion disease in animals and humans have demonstrated that these kinds of misfolded proteins can be a real threat to the public health in the world. Concomitantly, development of specific remedies for the diseases has been eagerly sought but has not been successfully achieved yet. Our research aims are based on these circumstances, and we are working on the above research themes to disclose the molecular mechanisms of the misfolded protein diseases, especially prion disease, and finally to make them curable.

Figure 1. Conceptual pathological pathway of brain disease caused by misfolded protein

Figure 1. Conceptual pathological pathway of brain disease caused by misfolded protein

Figure 2. Accumulated misfolded protein in prion disease mouse brain (PET blot)

Figure 2. Accumulated misfolded protein in prion disease mouse brain (PET blot)

Recent Publications

  • Hamanaka T, et al. Melanin or melanin-like substance interacts with the N-terminal portion of prion protein and inhibits abnormal prion protein formation in prion-infected cells. J. Virol.,in press
  • Teruya K, Doh-ura K. Insights from therapeutic studies for PrP prion disease. Cold Spring Harb. Perspect. Med., in press
  • Teruya K, et al. A single subcutaneous injection of cellulose ethers administered long before infection confers sustained protection against prion diseases in rodents. PLoS Pathog. 12:e1006045,2016
  • Hamanaka T, et al. Structure-activity analysis and antiprion mechanism of isoprenoid compounds. Virology. 486:63-70, 2015
  • Kimura T, et al. Secretin receptor involvement in prion-infected cells and animals. FEBS Lett. 589:2011-2018, 2015
  • Nishizawa K, et al. Efficacy and mechanism of a glycoside compound inhibiting abnormal prion protein formation in prion-infected cells. J. Virol. 88:4083-4099, 2014