| Budget Amount *help |
¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥29,510,000 (Direct Cost: ¥22,700,000、Indirect Cost: ¥6,810,000)
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| Outline of Final Research Achievements |
Familial amyloid polyneuropathy (FAP) is one of the hereditary amyloidoses caused by a point mutation in the human plasma protein, transthyretin (TTR). Amyloid fibrils derived from TTR variants accumulate in peripheral nerves and visceral organs, leading to inflammation-associated failure of multiple organs. TTR variants are easily dissociated from tetramer to monomer, which is the first step to amyloidosis, due to the low energetic stability of TTR variant tetrameric structure in comparison with wild-type (WT) TTR. We aimed to determine novel drugs that could either stabilize extracellular TTR tetramer or inhibit TTR secretion from the cells by high-throughput screening (HTS). Here, Western blotting- and Thioflavin-based biochemical assays identified thirteen compounds that stabilize the TTR tetramer as well as two TTR amyloid-solubilizing agents, and one inhibitor of TTR secretion from the cells were identified in this study.
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