beyond genetic factors in familial amyloidotic polyneuropathy protein glycation and the loss of fibrinogens chaperone activity除了遗传因素在家族amyloidotic多神经病蛋白糖化和纤维蛋白原的女伴活动的损失.pdfVIP

Beyond Genetic Factors in Familial Amyloidotic Polyneuropathy: Protein Glycation and the Loss of Fibrinogen’s Chaperone Activity 1 2 1 ´ 3 3 Gonc¸alo da Costa , Ricardo A. Gomes , Ana Guerreiro , Elia Mateus , Estela Monteiro , Eduardo 3 2,4 1 1 Barroso , Ana V. Coelho , Ana Ponces Freire , Carlos Cordeiro * ´ ´ ´ ´ ˆ 1 Centro de Quımica e Bioquımica, Departamento de Quımica e Bioquımica, Faculdade de Ciencias da Universidade de Lisboa, Lisboa, Portugal, 2 Instituto de Tecnologia ´ ´ ˜ ´ ´ Quımica e Biologica, Oeiras, Portugal, 3 Unidade de Transplantac¸ao Hepatica, Hospital Curry Cabral, Lisboa, Portugal, 4 Departamento de Quımica da Universidade de ´ ´ Evora, Evora, Portugal Abstract Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and so