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α-2-Macroglobulin (α-2M) is a homotetrameric serum protein consisting of four identical subunits that form dimers through disulfide bonds. Initially, α-2M was characterized as a pan-proteinase inhibitor that was able to bait proteinases into cleaving specific peptide sequences on α-2M. This interaction induces a conformational change in α-2M, thus enabling it to trap the proteinase and further inhibit its activity. Subsequently, α-2M has been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor β (TGFβ) in serum is primarily bound to α-2M, which renders TGFβ inactive. α-2M also binds to IL-6 and, thereby, increases the concentration of IL-6 near lymphocytes, hepatocytes and stem cells involved in mediating the inflammatory cascade. Mutations and deletions in the gene encoding α-2M are associated with an increased incidence of Alzheimer s disease (AD), which is consistent with the role of α-2M in mediating the clearance and degradation of A β, the major component of β-Amyloid deposits accumulated during AD.
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