Medical Institute of Bioregulation, Kyushu University

[Seminar in English]

Title

First-in-class drug development strategy for Parkinson’s disease via interruption of death signaling

Speaker

Dr. Eunhee Kim

Department of Biological Sciences, Chungnam National University, Daejeon 34134, Korea,
Visiting Professor, MIB

Date

Nov. 21 (Wed), 2018
15：00～16：30

Venue

Seminar Room, 1F, Main Building, Medical Institute of Bioregulation, Hospital Campus
No.31 on the following linked map.
（http://www.kyushu-u.ac.jp/f/33952/2018hospital_2-en.pdf）

Abstract

Fas-associated factor 1 (FAF1), a death–promoting protein, plays disease-promoting roles in neurodegenerative diseases, especially the Parkinson’s disease (PD). PD is the second most common neurodegenerative disease characterized by the selective loss of dopaminergic neurons. FAF1 expression was increased in the PD patients’ brains, leading us to explore FAF1’s role in the pathogenesis of PD. We identified FAF1 as a substrate of Parkin and found that FAF1 promotes α-synuclein accumulation, demonstrating the presence of Parkin–FAF1–α-synuclein signaling axis. FAF1 drove dopaminergic neuronal death by programmed necrosis as well as apoptosis upon oxidative stress. Such characteristic portrayed FAF1 as an advantageous drug target over proteins driving single type of cell death. Subsequently, we screened FAF1 inhibitory compounds and developed a compound targeting FAF1 (CTF), a first-in-class small molecule, and performed pre-clinical study. CTF demonstrated excellent efficacies in cell and in vivo models. At present, the molecule completed phase I clinical trial.

[This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI16C0947)]

Contact

Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation
Yusaku Nakabeppu
TEL: 092(642)6800