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In humans, and many other mammals, the predominant alpha-macroglobulin is alpha-2-macroglobulin (<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M), a tetrameric protein that is constitutively abundant in biological fluids (e.g., blood plasma, cerebral spinal fluid, synovial fluid, ocular fluid, and interstitial fluid).<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M is best known for its remarkable ability to inhibit a broad spectrum of proteases, but the full gamut of its activities affects diverse biological processes. For example,<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M can stabilise and facilitate the clearance of the Alzheimer\u2019s disease-associated amyloid beta (A<jats:italic>\u03b2<\/jats:italic>) peptide. Additionally,<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M can influence the signalling of cytokines and growth factors including neurotrophins. The results of several studies support the idea that the functions of<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M are uniquely regulated by hypochlorite, an oxidant that is generated during inflammation, which induces the native<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M tetramer to dissociate into dimers. This review will discuss the evidence for hypochlorite-induced regulation of<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>M and the possible implications of this in neuroinflammation and neurodegeneration.<\/jats:p>","DOI":"10.1155\/2019\/5410657","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T23:31:05Z","timestamp":1563838265000},"page":"1-9","source":"Crossref","is-referenced-by-count":80,"title":["Alpha-2-Macroglobulin, a Hypochlorite-Regulated Chaperone and Immune System Modulator"],"prefix":"10.1155","volume":"2019","author":[{"given":"Jordan H.","family":"Cater","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute and School of Chemistry and Molecular Bioscience, University of Wollongong, New South Wales 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical 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