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Title :家族性アミロイドポリニューロパチー原因蛋白質 transthyretin の細胞外分泌機構およびCr3+による transthyretin 四量体構造安定化作用の解明
Authors :佐藤, 卓史
Issue Date :25-Mar-2008
Abstract :Familial amyloid polyneuropathy (FAP) is one of hereditary amyloidoses caused by point mutation in the human plasma protein, transthyretin (TTR). Amyloid fibrils derived from TTR variants accumulate in peripheral nerves and visceral organs. TTR usually forms tetramer and functions as transporter of thyroxine (T4) and vitamin A by forming a complex with retinol-binding protein. TTR variants are easily dissociated from tetramer to monomer because of having low energetic stability of their tetrameric structure in comparison with wild-type (WT) TTR. Tetramer dissociation is the rate-limiting step for amyloidogenesis, and the natively folded monomer must first undergo partial denaturation to become insoluble aggregates and amyloid fibrils, which are the causative factors of peripheral polyneuropathy and visceral organ dysfunction. Although the mechanism of TTR amyloid fibril formation is elucidated as described above, the only treatment currently available for FAP is liver transplantation. Therefore, to develop a new treatment for FAP, we need to understand the pathogenesis of FAP from diversified perspectives, not only the mechanism of amyloid fibril formation. In this study, I investigated the following three issues to elucidate the pathogenesis of FAP and develop new treatment for FAP.
Type Local :博士論文
Publisher :熊本大学
URI :http://hdl.handle.net/2298/9379
Appears in Collections:Doctor of Pharmacy
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/9379