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The myelin‐associated glycoprotein inhibitor BENZ induces outgrowth and survival of rat dorsal root ganglion cell cultures
Author(s) -
Nowicki Marcin,
Kosacka Joanna,
Brossmer Reinhard,
SpanelBorowski Katharina,
Borlak Jürgen
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21422
Subject(s) - neurite , rhoa , dorsal root ganglion , cofilin , microbiology and biotechnology , myelin associated glycoprotein , chemistry , neurofilament , biology , cell , myelin , signal transduction , biochemistry , cytoskeleton , anatomy , in vitro , immunology , actin cytoskeleton , neuroscience , dorsum , central nervous system , immunohistochemistry
The novel myelin‐associated glycoprotein (MAG) inhibitor BENZ binds to the N ‐acetylneuraminic acid (Neu5Ac) portion of the N‐terminal Ig‐like domain of MAG. Treatment of rat dorsal root ganglion (DRG) cell cultures with BENZ‐induced outgrowth of neurofilament 200–positive neurites improved survival of neurons and increased the number of GFAP‐positive cells, as determined by fluorescence and confocal laser microscopy and by Western immunoblotting. Furthermore, treatment of DRG cell cultures with BENZ repressed gene and protein expression of the small GTPase RhoA but induced expression of Rho GTP–activating proteins 5 and 24, likely to counteract protein kinase A activity. Specifically, expression of inhibitors of neurite outgrowth, for example, Rock2 and PAK4, was repressed, but cofilin 1, a promoter of axonal growth, was induced. We propose that the MAG inhibitor BENZ abrogates the RhoA–ROCK–cofilin pathway to promote neurite outgrowth. Our findings require confirmation by in vivo animal studies. © 2007 Wiley‐Liss, Inc.