Development of small compound against polyglutamine diseases based on the chemical biology

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893065
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Shin Minkyoung 東京医科歯科大学, 難治疾患研究所, 助教 (60738566)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: ポリグルタミン / 神経変性疾患 / ケミカルバイオロジー

Outline of Final Research Achievements

Polyglutamine disease is a Hereditary neurodegenerative disease caused by a CAG repeat expansion in protein-coding portions of specific genes. Expanded CAG repeats are translated into a series of glutamine residues (polyQ) and are subject to increased aggregation. We previously identified a small compound (F7) that digests polyQ proteins.
In this study, we identified the target molecule for F7 chemical. The lack of this molecule increased polyQ accumulation, and its overexpression decreased it. We also indetified the involvement of autophagy machinery in the pharmacological effect of F7 chemical. We confirmed that F7 chemical improved the neurodegeneration observed in polyQ model mice.

Free Research Field

細胞生物学