2019 Fiscal Year Final Research Report
Investigation for the metabolic basis of ageing diversity
| Project/Area Number |
17H04150
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General internal medicine(including psychosomatic medicine)
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
横出 正之 京都大学, 医学研究科, 教授 (20252447)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | 老化 / 解糖系代謝 |
|---|
| Outline of Final Research Achievements |
Dysregulated glycolysis is also closely related to human pathological features (Mikawa T. et al, CMLS 2014). Impaired glycolysis in vivo is associated with dysfunction in various tissues, degenerative disorders, and diabetes. Conversely, the pathological enhancement of glycolysis is also observed in several diseased states, such as inflammation, ischemia, and the cancerous Warburg effect. We previously reported the proteolytic regulation of glycolytic enzyme PGAM under senescence-inducing stress (Mikawa et al, JCB 2014). Moreover, we identified nonenzymatic role of PGAM in global glycolytic regulation in cancerous condition, but not in standard cells. PGAM interacts with Chk1 kinase, to cooperate for glycolytic regulation.
|
| Free Research Field |
老化生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
従来、ワールブルグ効果（癌での解糖系亢進）の発見以来、解糖系阻害剤の癌治療への応用は長く期待されてきた。従来の代謝阻害剤は、「活性中心」と呼ばれる代謝酵素活性部位に結合し薬理作用を発揮するようデザインされてきた。しかしながら、解糖系代謝は正常細胞でも生理的必須機能を担っており、全身への重篤な副作用の観点から、単なる代謝阻害は、癌治療として有効性確立や実用化展開が難しい (Granchi et al,Chem Med Chem. 2012)。解糖系代謝調節剤が期待されながらも、長く実現化しない理由である。本研究の成果は、長く実現不可能と言われた解糖系代謝調節による抗癌剤開発に道を開くものである。
|
