Molecular interactions in the formation and deposition of beta2-microglobulin-related amyloid fibrils.
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.
Naiki
Hironobu
H
Division of Molecular Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. naiki@fmsrsa.fukui-med.ac.jp
Yamamoto
Suguru
S
Hasegawa
Kazuhiro
K
Yamaguchi
Itaru
I
Goto
Yuji
Y
Gejyo
Fumitake
F
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D013501:Surface-Active Agents / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism*
D000682:Amyloid; D013501:Surface-Active Agents; D001613:beta 2-Microglobulin