Establishment of a molecular therapy for the polyglutamine diseases targeting toxic oligomers
| Project/Area Number |
24591287
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Tokyo Medical University (2013-2015)
独立行政法人国立精神・神経医療研究センター (2012) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 神経変性疾患 / ポリグルタミン病 / 治療薬開発 / オリゴマー |
|---|
| Outline of Final Research Achievements |
Recent studies have demonstrated that in many neurodegenerative diseases, including Alzheimer disease and the polyglutamine (polyQ) diseases, neurodegeneration results from the actions of a toxic oligomeric species of the mutant protein. In this study, we analyzed the effects of QAI1, a small chemical compound inhibitor of polyQ protein oligomers that we previously identified. We analyzed the pharmacokinetics of QAI1 in mice, as well as the therapeutic effects of QAI1 on the neurological phenotypes and histological phenotypes of two mouse models of the polyQ diseases.
We found that QAI1 effectively enters the brain upon its oral administration in mice. Furthermore, oral administration of QAI1 was shown to alleviate the neurological phenotypes and histological phenotypes of 2 mouse models of the polyQ diseases. Our results demonstrated the potential of QAI1 as a therapeutic molecule for the polyQ diseases.
|
Report
(5 results)
Research Products
(8 results)
-
-
[Journal Article] p62 plays a protective role in the autophagic degradation of polyglutamine protein oligomers in polyglutamine disease model flies.2015
Author(s)
Saitoh Y, Fujikake N, Okamoto Y, Popiel HA, Hatanaka Y, Ueyama M, Suzuki M, Gaumer S, Murata M, Wada K, Nagai Y.
-
Journal Title
J Biol Chem
Volume: 290
Issue: 3
Pages: 1442-53
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Presentation] Identification of a polyglutamine oligomerization inhibitor with high brain permeability and safety, which exerts therapeutic effects on multiple mouse models of the polyglutamine diseases2013
Author(s)
H.A. Popiel, H. Yamane, T. Takahashi, M. Tada, Y. Saitoh, H. Fujita, Y. Okamoto, T. Toda, K. Wada, O. Onodera, Y. Nagai
Organizer
Gordon Research Conference on CAG Triplet Repeat Disorders
Place of Presentation
Waterville Valley, USA
Related Report
-
-
