Alpha‐2‐macroglobulin: A physiological guardian

Abstract

Alpha macroglobulins are large glycoproteins which are present in the body fluids of both invertebrates and vertebrates. Alpha-2-macroglobulin (α2 M), a key member of alpha macroglobulin superfamily, is a high-molecular weight homotetrameric glycoprotein. α2 M has many diversified and complex functions, but it is primarily known by its ability to inhibit a broad spectrum of proteases without the direct blockage of the protease active site. α2 M is also known to be involved in the regulation, transport, and a host of other functions. For example, apart from inhibiting proteinases, it regulates binding of transferrin to its surface receptor, binds defensin and myelin basic protein, etc., binds several important cytokines, including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and modify their biological activity. α2 M also binds a number of hormones and regulates their activity. α2 M is said to protect the body against various infections, and hence, can be used as a biomarker for the diagnosis and prognosis of a number of diseases. However, this multipurpose antiproteinse is not "fail safe" and could be damaged by reactive species generated endogenously or exogenously, leading to various pathophysiological conditions.

Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

“…However, ␣ 2 -macroglobulin is produced mainly by hepatocytes in the liver, and only in small amounts by cells in the lungs (13). Moreover, a primary role of ␣ 2 -macroglobulin is to rapidly trap excess proteinases, but not to inactivate them, so proteases can still be released after binding ␣ 2 -macroglobulin (62,72). Unlike ␣ 2 -macroglobulin, ␣ 1 -AT is more likely to be a physiological inactivator of elastase.…”

Identification and Functional Analysis of Differentially Expressed Genes Related to Metastatic Osteosarcoma

“…In general, A2M is a high-molecular weight homotetrameric glycoprotein and functions as a physiological guardian (Rehman et al, 2013). Many researches focus on its function in the Alzheimer's disease and depression (Blennow et al, 2000;Fujita et al, 2003), and few are in cancer even OS.…”

Unraveling the genes implicated in Alzheimer's disease

“…The A2M gene encodes A2M, and it inhibits numerous proteases, such as trypsin, thrombin and collagenase (48). A2M acts as an extracellular chaperone and is involved in the clearance of extracellular Aβ (49,50).…”