| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
For “the vacuole-like abnormal intracellular structure” (our finding) which is generated when an anion transport protein SLC4A2 is coexpressed with optineurin (OPTN) and “the OPTN granules” which is induced in cultured cells by the glaucomatous OPTN mutation E50K, we analyzed the signaling pathway, formation difference between ALS- and glaucomatous-mutation, and, the cellular localization.
In addition, we found that these phenomena related to the abnormal protein accumulation were suppressed by induction of autophagy. This effect was also observed in case of the intracellular inclusion generated by another ALS-causative gene TARDBP. It was reported that OPTN is detected in the inclusion bodies of ALS patients’ nerve cells caused by SOD1 or TARDBP mutation. It suggested that over-accumulation of abnormal protein or decreasing of autophagy function of OPTN by mutation is possible disease onset mechanism and that inducing autophagy possibly suppresses the onset of ALS and glaucoma.
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