{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:19:44Z","timestamp":1762100384345},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T00:00:00Z","timestamp":1097452800000},"content-version":"vor","delay-in-days":4576,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[1992,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b12\u2010Macroglobulin (\u03b1<jats:sub>2<\/jats:sub>M) is a rather ubiquitous protein in extracellular spaces of mammals. It is an inhibitor of endopeptidases, can be modified by aliphatic amines, and combines with a number of hormones\/cytokines such as \u03b2\u2010nerve growth factor (NGF) [Koo PH, Stach RW (1989): J Neurosci Res 22:247]. The objective of this study is to compare the NGF\u2010binding properties of methylamine\u2010modified human \u03b1<jats:sub>2<\/jats:sub>M (MA\u2010\u03b1<jats:sub>2<\/jats:sub>M) versus normal \u03b1<jats:sub>2<\/jats:sub>M and their effects on the biological activity of NGF and neurite extension by embryonic chicken dorsal root ganglia. As determined by gel filtration, polyacrylamide gel electrophoresis, and equilibrium binding studies, these two forms of \u03b1<jats:sub>2<\/jats:sub>M are similar in their binding affinities, with MA\u2010\u03b1<jats:sub>2<\/jats:sub>M binding about twice as much NGF as normal \u03b1<jats:sub>2<\/jats:sub>M. Both normal \u03b1<jats:sub>2<\/jats:sub>M and MA \u03b1<jats:sub>2<\/jats:sub>M combine noncovalently with NGF, and prior modification of \u03b1<jats:sub>2<\/jats:sub>M is unnecessary for the binding to occur. In contrast to normal \u03b1<jats:sub>2<\/jats:sub>M, MA\u2010\u03b1<jats:sub>2<\/jats:sub>M potently inhibits the biological activity of NGF and exerts a dose\u2010dependent inhibition on the NGF\u2010stimulated neurite outgrowth by embryonic chicken dorsal root ganglia in culture. The inhibitory effect of MA\u2010\u03b1<jats:sub>2<\/jats:sub>M can be overcome by higher NGF concentrations, but is irreversible at lower NGF concentrations. Trypsin\u2010modified \u03b1<jats:sub>2<\/jats:sub>M combines covalently and noncovalently with more NGF than normal \u03b1<jats:sub>2<\/jats:sub>M but has very little neurite inhibitory activity. The mechanism of inhibition by MA\u2010\u03b1<jats:sub>2<\/jats:sub>M is discussed.<\/jats:p>","DOI":"10.1002\/jnr.490310412","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T18:42:07Z","timestamp":1117305727000},"page":"678-692","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of nerve growth factor\u2010stimulated neurite outgrowth by methylamine\u2010modified \u03b1<sub>2<\/sub>\u2010macroglobulin"],"prefix":"10.1002","volume":"31","author":[{"given":"P. H.","family":"Koo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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