Developing New Medicine for Dementia

Introduction

   The molecular characterization of a protein is my favorite, using biophysical-, biochemical- and molecular biological-methods. Now analysing the molecular interaction between lead chemicals and target using X-ray crystallography to choose higher affinity compounds.

   We are focusing on metabolic enzymes of tryptophan pathway (IDO and TDO) and tau protein as target because some metabolic products of tryptophan have been suggested to relate on neuronal disorder and also because because tau seems to be involved in the neurofibrillary tangle formation in AD brain. Although extensive trial of crystallization of the tau protein has been done, never achieved.

   We will contribute to explain the aggregation mechanism and to find inhibitor chemicals using precise analysis of the X-ray crystallography of tau protein.

Research

Link

Contact

Ken Okada, PhD

Lab Drug Screening, Dep Drug discovery,

Center for Development of Advanced Medicine for Dementia (CAMD)

National Center for Geriatrics and Gerontology

35 Gengo, Morioka-cho, Obu-City,
Aichi 474-8511, Japan

e-mail:

Access: (-->access map)

Manuscripts

ºOkada K, Angkawidjaja C, Koga Y, Kanaya S. Structural and mechanistic insights into the kynurenine aminotransferase-mediated excretion of kynurenic acid. Journal of Structural Biology, 185:257-266, 2014
ºOkada K, Angkawidjaja C, Koga Y, Takano K, Kanaya S. Characteristic features of kynurenine aminotransferase allosterically regulated by (alpha)-ketoglutarate in cooperation with kynurenine. PLoS One. 7:e40307, 2012.
Conference
Mikawa R, Okuno A, Yoshimi T, ºOkada K, Takayanagi A, Takikawa O. Implication of Brain Microvessel Endothelial Cell-derived Beta-Amyloid Peptide in Cerebral Amyloid Angiopathy Associated with Alzheimer's Disease. Alzheimer's Association International Conference (AAIC) 2013, July 14, Boston, USA.
Okuno A, Yoshimi T, ºOkada K, Mikawa R, Takayanagi A, Takikawa O. Pathogenic role of IDO in Alzheimer's disease : Astrocytes but not neurons are responsible for the increase of amyloid β peptide induced by neurotoxin quinolinic acid. 13th International Conference of Tryptophan Research, November 7, 2012, Sydney, Australia.