2023 Fiscal Year Final Research Report
Elucidation of the pathological mechanism of Niemann-Pick disease type C caused by abnormalities in ceramide metabolism and drug discovery
| Project/Area Number |
21H02631
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47040:Pharmacology-related
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | セラミド代謝酵素 / ニーマン・ピック病C型 |
|---|
| Outline of Final Research Achievements |
Niemann-Pick disease type C (NPC) is a lipid storage disorder resulting from mutations in either the NPC1 or NPC2 genes. Loss of function of NPC1 or NPC2 protein causes defects in the intracellular cholesterol trafficking, which results in the accumulation of multiple lipid species in the endosomal/lysosomal compartment. Miglustat has been shown to increase lifespan, delay the onset of neurological dysfunction, and reduce the magnitude of neurological symptoms in NPC animal models, but the therapeutic benefit is limited. In this study, we revealed that ceramide-metabolizing enzymes can be a therapeutic target for NPC. Furthermore, we attempted to develop a ceramide-metabolizing enzyme inhibitor to develop a therapeutic drug for NPC and obtained a new compound.
|
| Free Research Field |
薬理学、脂質生化学
|
| Academic Significance and Societal Importance of the Research Achievements |
セラミド代謝酵素がNPCの治療標的となり得ることを明らかにし、また、セラミド代謝酵素を阻害する新規化合物を得ることに成功した。本研究で着目しているセラミド代謝酵素の阻害は遊離コレステロールの蓄積を軽減でき、また、副作用も少ないことが期待される。従って、今後さらなる誘導体展開を実施することで、これまでにない革新的なNPC治療薬が創出されることが期待される。
|
