Molecular interactions in the formation and deposition of beta2-microglobulin-related amyloid fibrils

Amyloid. 2005 Mar;12(1):15-25. doi: 10.1080/13506120500032352.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Amyloidosis / metabolism*
  • Amyloidosis / pathology
  • Humans
  • Surface-Active Agents / pharmacology
  • beta 2-Microglobulin / chemistry
  • beta 2-Microglobulin / metabolism*

Substances

  • Amyloid
  • Surface-Active Agents
  • beta 2-Microglobulin