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Systemic amyloidosis: lessons from β2-microglobulin.

Stoppini M, Bellotti V - J. Biol. Chem. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and.

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Related in: MedlinePlus

Tapping mode atomic force microscopy image of β2-m amyloid fibers in the presence of fibrillar collagen and heparin. Shown is the fibril network connecting isolated collagen fibrils, observed after 24 h of incubation. Non-fibrillar aggregates are also present. Amplitude data: scan size, 5.7 μm. This figure was originally published in The Journal of Biological Chemistry (Relini, A., De Stefano, S., Torrassa, S., Cavalleri, O., Rolandi, R., Gliozzi, A., Giorgetti, S., Raimondi, S., Marchese, L., Verga, L., Rossi, A., Stoppini, M., and Bellotti, V. (2008) Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. J. Biol. Chem.283, 4912–4920. © the American Society for Biochemistry and Molecular Biology).
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Figure 1: Tapping mode atomic force microscopy image of β2-m amyloid fibers in the presence of fibrillar collagen and heparin. Shown is the fibril network connecting isolated collagen fibrils, observed after 24 h of incubation. Non-fibrillar aggregates are also present. Amplitude data: scan size, 5.7 μm. This figure was originally published in The Journal of Biological Chemistry (Relini, A., De Stefano, S., Torrassa, S., Cavalleri, O., Rolandi, R., Gliozzi, A., Giorgetti, S., Raimondi, S., Marchese, L., Verga, L., Rossi, A., Stoppini, M., and Bellotti, V. (2008) Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. J. Biol. Chem.283, 4912–4920. © the American Society for Biochemistry and Molecular Biology).

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.


Systemic amyloidosis: lessons from β2-microglobulin.

Stoppini M, Bellotti V - J. Biol. Chem. (2015)

Tapping mode atomic force microscopy image of β2-m amyloid fibers in the presence of fibrillar collagen and heparin. Shown is the fibril network connecting isolated collagen fibrils, observed after 24 h of incubation. Non-fibrillar aggregates are also present. Amplitude data: scan size, 5.7 μm. This figure was originally published in The Journal of Biological Chemistry (Relini, A., De Stefano, S., Torrassa, S., Cavalleri, O., Rolandi, R., Gliozzi, A., Giorgetti, S., Raimondi, S., Marchese, L., Verga, L., Rossi, A., Stoppini, M., and Bellotti, V. (2008) Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. J. Biol. Chem.283, 4912–4920. © the American Society for Biochemistry and Molecular Biology).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400370&req=5

Figure 1: Tapping mode atomic force microscopy image of β2-m amyloid fibers in the presence of fibrillar collagen and heparin. Shown is the fibril network connecting isolated collagen fibrils, observed after 24 h of incubation. Non-fibrillar aggregates are also present. Amplitude data: scan size, 5.7 μm. This figure was originally published in The Journal of Biological Chemistry (Relini, A., De Stefano, S., Torrassa, S., Cavalleri, O., Rolandi, R., Gliozzi, A., Giorgetti, S., Raimondi, S., Marchese, L., Verga, L., Rossi, A., Stoppini, M., and Bellotti, V. (2008) Heparin strongly enhances the formation of β2-microglobulin amyloid fibrils in the presence of type I collagen. J. Biol. Chem.283, 4912–4920. © the American Society for Biochemistry and Molecular Biology).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and.

Show MeSH
Related in: MedlinePlus