Naiki Hironobu, Yamamoto Suguru, Hasegawa Kazuhiro, Yamaguchi Itaru, Goto Yuji, Gejyo Fumitake
Division of Molecular Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Amyloid. 2005 Mar;12(1):15-25. doi: 10.1080/13506120500032352.
In beta2-microglobulin-related (A beta2M) amyloidosis, a serious complication in patients on long-term dialysis, partial unfolding of beta2-microglobulin (beta2-m) is believed to be prerequisite to its assembly into A beta2M amyloid fibrils. Many kinds of amyloid-associated molecules, (e.g., apolipoprotein E (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the development of A beta2M amyloidosis. In 1990s, the formation of A beta2M amyloid fibrils in vitro was first observed at low pH (2.0-3.0). Very recently, low concentrations of 2,2,2-trifluoroethanol (TFE) and the sub-micellar concentration of sodium dodecyl sulfate, a model for anionic phospholipids, have been reported to cause the extension of A beta2M amyloid fibrils at a neutral pH, inducing partial unfolding of beta2-m and stabilization of the fibrils. Moreover, apoE, GAGs, and PGs were found to stabilize A beta2M amyloid fibrils at a neutral pH, forming a stable complex with the fibrils. Some GAGs, especially heparin, enhanced the fibril extension in the presence of TFE at a neutral pH. Some PGs, especially biglycan also induced the polymerization of acid-denatured beta2-m. These findings are consistent with the hypothesis that in vivo, specific molecules that affect the conformation and stability of beta2-m and amyloid fibrils will have significant effects on the deposition of A beta2M amyloid fibrils.
在β2-微球蛋白相关（Aβ2M）淀粉样变性中，这是长期透析患者的一种严重并发症，β2-微球蛋白（β2-m）的部分解折叠被认为是其组装成Aβ2M淀粉样纤维的先决条件。许多种淀粉样相关分子，（例如，载脂蛋白E（apoE）、糖胺聚糖（GAGs）、蛋白聚糖（PGs））可能促成Aβ2M淀粉样变性的发展。在20世纪90年代，首次在低pH（2.0 - 3.0）条件下观察到体外Aβ2M淀粉样纤维的形成。最近，有报道称低浓度的2,2,2-三氟乙醇（TFE）和十二烷基硫酸钠的亚胶束浓度（一种阴离子磷脂模型）可在中性pH条件下导致Aβ2M淀粉样纤维的延长，诱导β2-m的部分解折叠并使纤维稳定。此外，发现apoE、GAGs和PGs可在中性pH条件下稳定Aβ2M淀粉样纤维，与纤维形成稳定的复合物。一些GAGs，尤其是肝素，在中性pH条件下存在TFE时可增强纤维的延长。一些PGs，尤其是双糖链蛋白聚糖也可诱导酸变性β2-m的聚合。这些发现与以下假设一致，即在体内，影响β2-m和淀粉样纤维构象及稳定性的特定分子将对Aβ2M淀粉样纤维的沉积产生显著影响。
