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Publication : Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin.

First Author  Lebeurrier N Year  2008
Journal  J Cell Sci Volume  121
Issue  Pt 20 Pages  3357-65
PubMed ID  18796535 Mgi Jnum  J:142576
Mgi Id  MGI:3821787 Doi  10.1242/jcs.031872
Citation  Lebeurrier N, et al. (2008) Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin. J Cell Sci 121(Pt 20):3357-65
abstractText  The balance between tissue-type plasminogen activator (tPA) and one of its inhibitors, neuroserpin, has crucial roles in the central nervous system, including the control of neuronal migration, neuronal plasticity and neuronal death. In the present study, we demonstrate that the activation of the transforming growth factor-beta (TGFbeta)-related BMPR-IB (also known as BMPR1B and Alk6)- and Smad5-dependent signalling pathways controls neuroserpin transcription. Accordingly, we demonstrate for the first time that anti-Mullerian hormone (AMH), a member of the TGFbeta family, promotes the expression of neuroserpin in cultured neurons but not in astrocytes. The relevance of these findings is confirmed by the presence of both AMH and AMH type-II receptor (AMHR-II) in brain tissues, and is supported by the observation of reduced levels of neuroserpin in the brain of AMHR-II-deficient mice. Interestingly, as previously demonstrated for neuroserpin, AMH protects neurons against N-methyl-D-aspartate (NMDA)-mediated excitotoxicity both in vitro and in vivo. This study demonstrates the existence of an AMH-dependent signalling pathway in the brain leading to an overexpression of the serine-protease inhibitor, neuroserpin, and neuronal survival.
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