Maury C P
Fourth Department of Medicine, University of Helsinki, Finland.
J Clin Invest. 1991 Apr;87(4):1195-9. doi: 10.1172/JCI115118.
The Finnish type of familial amyloidosis is a systemic disease characterized by progressive cranial neuropathy, corneal lattice dystrophy, and distal sensimotor neuropathy. Amyloid fibrils were isolated from the kidney and heart of a patient with Finnish amyloidosis. After solubilization, the amyloid proteins were fractionated by gel filtration and purified by reverse-phase HPLC. Complete amino acid sequence analyses show that the two amyloid components obtained are fragments of gelsolin, an actin-modulating protein occurring in plasma and the cytoskeleton. The larger component represents residues 173-243 and the minor component residues 173-225, respectively, of mature gelsolin. When compared with the predicted primary structure of human gelsolin a single amino acid substitution is present in amyloid: at position 15 of the amyloid proteins an asparagine is found instead of an aspartic acid residue at the corresponding position (187) in gelsolin. Antibodies to a dodecapeptide of the amyloidogenic region of gelsolin specifically stain the tissue amyloid deposits in Finnish hereditary amyloidosis. The results show that the amyloid subunit protein in Finnish hereditary amyloidosis represents a new type of amyloid that is derived from an actin filament-binding region of a variant gelsolin molecule by limited proteolysis.
芬兰型家族性淀粉样变性是一种全身性疾病，其特征为进行性颅神经病变、角膜格子状营养不良和远端感觉运动神经病变。从一名芬兰淀粉样变性患者的肾脏和心脏中分离出淀粉样纤维。溶解后，通过凝胶过滤对淀粉样蛋白进行分级分离，并通过反相高效液相色谱法进行纯化。完整的氨基酸序列分析表明，所获得的两种淀粉样成分是凝溶胶蛋白的片段，凝溶胶蛋白是一种存在于血浆和细胞骨架中的肌动蛋白调节蛋白。较大的成分分别代表成熟凝溶胶蛋白的第173 - 243位残基，较小的成分代表第173 - 225位残基。与人类凝溶胶蛋白的预测一级结构相比，淀粉样蛋白中存在一个单氨基酸取代：在淀粉样蛋白的第15位，发现一个天冬酰胺，而在凝溶胶蛋白的相应位置（187位）是一个天冬氨酸残基。针对凝溶胶蛋白淀粉样生成区域的十二肽的抗体特异性地标记芬兰遗传性淀粉样变性中的组织淀粉样沉积物。结果表明，芬兰遗传性淀粉样变性中的淀粉样亚基蛋白代表一种新型淀粉样蛋白，它是通过有限的蛋白水解作用从变异凝溶胶蛋白分子的肌动蛋白丝结合区域衍生而来的。
