Systemic amyloidosis: lessons from β2-microglobulin.
Bottom Line: Its genetic variant D76N causes a very rare form of familial systemic amyloidosis.These two types of amyloidoses differ significantly in terms of the tissue localization of deposits and for major pathological features.Considering how the amyloidogenesis of the β2-microglobulin mechanism has been scrutinized in depth for the last three decades, the comparative analysis of molecular and pathological properties of wild type β2-microglobulin and of the D76N variant offers a unique opportunity to critically reconsider the current understanding of the relation between the protein's structural properties and its pathologic behavior.
Affiliation: From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and.Show MeSH
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Mentions: The discovery that in vitro truncated β2-m can form amyloid fibrils, in a physiologic environment, has moved the methods of in vitro fibrillogenesis toward more bio-compatible conditions. A successful example of a bridge between the known tropism of β2-m for the muscle skeletal system and an in vitro method was achieved by studying the effect of type I and type II collagen on β2-m amyloidogenesis (31). The effect of the interaction of β2-m with the collagen's surface is remarkable, and Fig. 1 illustrates a representative image of the growth of amyloid fibrils stemming from type I collagen fibers. The presence of β2-m oligomers and GAGs was able to accelerate the process of the amyloid grown on the collagen surface. This confirmed the generic pro-amyloidogenic effect played by the aforementioned components in fibrillogenesis (32). However, despite the growth of fibrils on the collagen surface, in the absence of fluid flow, the majority of the bulk of WT β2-m in solution was not converted into fibrils on a time scale of several days.
Affiliation: From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and.