Modulation of gamma-secretase and autophagy in optic nerve axonal degeneration
Project/Area Number |
24592683
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
|
Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
KITAOKA YASUSHI 聖マリアンナ医科大学, 医学部, 准教授 (10367352)
|
Co-Investigator(Renkei-kenkyūsha) |
MUNEMASA Yasunari 聖マリアンナ医科大学, 医学部, 講師 (30440340)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | γセクレターゼ / 緑内障 / TNF / オートファジー / 視神経 / 軸索変性 / 眼薬理学 / 軸索保護 / アルツハイマー病 / プレセニリン / APP / GFAP |
Outline of Final Research Achievements |
Axonal degeneration precedes retinal ganglion cell death in TNF-induced optic nerve degeneration model. We observed that phosphorylated-presenilin1 (p-PS1) was increased in the optic nerve after TNF injection and was found to colocalize with vimentin and glial fibrillary acidic protein, markers of astrocytes. Immunoprecipitation using 6E10 antibody revealed an increase in γ-secretase activation in the optic nerve after TNF injection, which was inhibited by treatment with the γ-secretase inhibitor. Moreover, γ-secretase inhibition significantly prevented the loss of axons in the optic nerve after TNF injection. Modulation of γ-secretase activity may be useful for the treatment of TNF-related optic neuropathy. p62 is involved in autophagy machinery. We observed that p62 was increased in the optic nerve degeneration. Activation of autophagy decreased p62 protein levels and leaded to axonal protection.
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Report
(4 results)
Research Products
(19 results)