Comprehensive analysis of the pathogenic mechanism of GM2 gangliosidoses involving neurological symptoms by focusing on transcriptomes including ncRNA
| Project/Area Number |
26860037
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
IKUO Mariko 徳島大学, 大学院医歯薬学研究部(薬学系), 特任助教 (60713401)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | リソソーム病 / レクチン / ミクログリア / マクロファージ / GM2蓄積症 / 中枢神経疾患 / 炎症 / 免疫 / 糖鎖 |
|---|
| Outline of Final Research Achievements |
GM2 gangliosidosis (ex. Sandhoff disease (SD)) is caused by genetic mutations in HexA enzyme coding genes. HexA disruption results in lysosomal storage of substrates such as GM2 gangliosides. We performed microarray analysis for SD model mice brain and determined RNA expression profile change. We focused on the up-regulation of A lectin that activates complement pathway. The lectin is localized in Purkinje cells and up-regulated in microglia that belong to F4/80 positive macrophage linage. The lectin mRNA expression was elaborated in brain and liver of SD mice and not in spleen, kidney nor lung. This pattern was correlated with F4/80 mRNA, but not with CD68, another macrophage marker that also expressed in F4/80 negative macrophage linage. HexA enzyme replacement for SD microglia cells lowered the lectin mRNA expression. The lectin that expression correlates with HexA expression is a potent biomarker for GM2 gangliosidosis.
|
Report
(4 results)
Research Products
(5 results)
-
-
-
-
[Presentation] Development of protease-resisitant modified human beta-hexosaminidase B and evaluation of intracerebroventricular replacement effects on GM2 gangliosidosis model mice.,2015
Author(s)
Kitakaze Keisuke, Tasaki Chikako, Mizutani Yasumichi, Sugiyama Eiji, Mariko Ikuo, kamiya Mako, Setou Mitsutoshi, Urano Yasuteru and Kouji Itou
Organizer
The 11th Annual World Symposium
Place of Presentation
Hyatt Regency Orlando (Orlando, FL, USA)
Year and Date
2015-02-09 – 2015-02-13
Related Report
-
