Systemic amyloidosis: lessons from β2-microglobulin.
β2-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. 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.
From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and.
Monica
M
Stoppini
From the Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, 27100 Pavia, Italy and the Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London NW3 2PF, United Kingdom v.bellotti@ucl.ac.uk vbellot@unipv.it.
Vittorio
V
Bellotti
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000686:Amyloidosis / Q000145:classification / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000517:prevention & control*; D011487:Protein Conformation; D006435:Renal Dialysis / Q000009:adverse effects; D057127:Single-Chain Antibodies / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
D000682:Amyloid; D057127:Single-Chain Antibodies; D001613:beta 2-Microglobulin; D004318:Doxycycline
Amyloid; Atomic Force Microscopy (AFM); Fibrillogenesis in Vitro; Genetic Variant Asp76Asn; Mechanism of Amyloidogenesis; Protein Aggregation; Protein Misfolding; Protein Structure; β2-Microglobulin