Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Outline of Final Research Achievements |
The aim of this project is to develop therapeutic interventions against protein aggregation diseases. Mutations within the alphaB-crystallin (aBC) gene are linked to crystallinopathy, characterized by intracellular accumulation of protein aggregates. We previously demonstrated that enforced expression of aBC on the endoplasmic reticulum (ER) prevented aggregation of the R120G aBC mutant, suggesting that manipulation of the ER-anchored aBC (ERaBC) target is effective for protein aggregation diseases. In this study, CLN6, an ER transmembrane protein, was isolated as an ERaBC binder. We revealed that CLN6 not only mediates the anti-aggregate activity of ERaBC but also prevents the R120G mutant from aggregating independently of ERaBC. CLN6 profoundly inhibited aggregation of the ALS-associated TDP-43 variant as well. Overall, we conclude that dictating CLN6 would be a promising strategy for a wide array of protein aggregation diseases.
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