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Serpini1  -  serine (or cysteine) peptidase inhibitor,...

Mus musculus

Synonyms: AI837402, Neuroserpin, Ns, PI-12, PI12, ...
 
 
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Disease relevance of Serpini1

  • Neuroserpin (PI12), initially identified as an axonally secreted protein in cultured chicken dorsal root ganglion neurons, belongs to the serpin family of the serine protease inhibitors and is mainly expressed by neurons of both the developing and the adult nervous system [1].
  • Here, we aimed at determining the mechanisms of action responsible for the previously reported neuroprotective activity of NS in rodent experimental cerebral ischemia [2].
  • Altogether, these data suggest that an overexpression of neuroserpin in the brain parenchyma might limit the deleterious effect of tPA on NMDA receptor-mediated neuronal death, which occurs following experimental ischemia [2].
  • In addition to shedding light on the pathophysiology of the human disorder, these mice provide an excellent model to study mechanisms of neurodegeneration or establish novel therapies for familial encephalopathy with neuroserpin inclusion bodies and other neurodegenerative diseases with intracellular protein deposition [3].
 

Psychiatry related information on Serpini1

 

High impact information on Serpini1

  • Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent [5].
  • Inhibition of tPA within the hippocampus by neuroserpin treatment does not prevent seizure onset but instead markedly delays the progression of seizure activity in both rats and wild-type mice [5].
  • Specifically, seizure induction by KA injection into the amygdala induces tPA activity and cell death in both hippocampi, and unilateral treatment of rats with neuroserpin, a natural inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi [5].
  • During embryonic development, neuroserpin mRNA was not detectable in neuroepithelia, but it was expressed in the differentiating fields of most CNS regions concurrent with their appearance [6].
  • In the cerebellum, the granule cells and a subgroup of Purkinje cells were neuroserpin-positive during postnatal development [6].
 

Chemical compound and disease context of Serpini1

 

Biological context of Serpini1

  • The murine neuroserpin gene spans over more than 55kb and consists of nine exons [1].
  • A reactive site mutant of neuroserpin neither formed complexes with nor inhibited the amidolytic activity of any of the tested proteinases [7].
  • They showed reduced center exploration in the open-field test and, like neuroserpin-deficient mice, a neophobic phenotype in the novel object test [8].
  • To investigate the effect of neuroserpin on the size and the histology of the infarct we produced transgenic mice overexpressing neuroserpin approximately sixfold in the nervous system [9].
  • Because recent studies have indicated that tissue plasminogen activator (tPA) aggravates neurodegenerative processes in many neural pathologies, we studied whether the endogenous tPA antagonist neuroserpin has a neuroprotective effect in an animal model of focal ischemic stroke [9].
 

Anatomical context of Serpini1

 

Associations of Serpini1 with chemical compounds

  • Neuroserpin is an axonally secreted serine proteinase inhibitor that is expressed in neurons during embryogenesis and in the adult nervous system [7].
  • First, we show in vivo that exogenous NS protects the cortex and the striatum against NMDA-induced injury [2].
  • Here we demonstrate that neuroserpin expression is regulated by thyroid hormone (T3) [11].
  • 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 [12].
 

Physical interactions of Serpini1

  • Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin [7].
 

Regulatory relationships of Serpini1

  • Mice overexpressing neuroserpin under the control of the Thy1.2 promoter are known to have a reduced brain tPA activity [8].
 

Other interactions of Serpini1

  • The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo [2].
  • From among these GD-specific genes, we confirmed the expression of Serpini1 and Rab33a in P19 differentiation models and adult brains [13].
  • Mutations in the neuroserpin gene cause protein polymerization and formation of inclusion bodies leading to progressive myoclonic epilepsy and neurodegeneration [11].

References

  1. Structure of the mouse gene for the serine protease inhibitor neuroserpin (PI12). Berger, P., Kozlov, S.V., Krueger, S.R., Sonderegger, P. Gene (1998) [Pubmed]
  2. The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. Lebeurrier, N., Liot, G., Lopez-Atalaya, J.P., Orset, C., Fernandez-Monreal, M., Sonderegger, P., Ali, C., Vivien, D. Mol. Cell. Neurosci. (2005) [Pubmed]
  3. Accumulation of mutant neuroserpin precedes development of clinical symptoms in familial encephalopathy with neuroserpin inclusion bodies. Galliciotti, G., Glatzel, M., Kinter, J., Kozlov, S.V., Cinelli, P., Rülicke, T., Sonderegger, P. Am. J. Pathol. (2007) [Pubmed]
  4. Expression of neuroserpin in the visual cortex of the mouse during the developmental critical period. Wannier-Morino, P., Rager, G., Sonderegger, P., Grabs, D. Eur. J. Neurosci. (2003) [Pubmed]
  5. Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent. Yepes, M., Sandkvist, M., Coleman, T.A., Moore, E., Wu, J.Y., Mitola, D., Bugge, T.H., Lawrence, D.A. J. Clin. Invest. (2002) [Pubmed]
  6. Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse. Krueger, S.R., Ghisu, G.P., Cinelli, P., Gschwend, T.P., Osterwalder, T., Wolfer, D.P., Sonderegger, P. J. Neurosci. (1997) [Pubmed]
  7. The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. Osterwalder, T., Cinelli, P., Baici, A., Pennella, A., Krueger, S.R., Schrimpf, S.P., Meins, M., Sonderegger, P. J. Biol. Chem. (1998) [Pubmed]
  8. Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Madani, R., Kozlov, S., Akhmedov, A., Cinelli, P., Kinter, J., Lipp, H.P., Sonderegger, P., Wolfer, D.P. Mol. Cell. Neurosci. (2003) [Pubmed]
  9. Neuroserpin, a neuroprotective factor in focal ischemic stroke. Cinelli, P., Madani, R., Tsuzuki, N., Vallet, P., Arras, M., Zhao, C.N., Osterwalder, T., Rülicke, T., Sonderegger, P. Mol. Cell. Neurosci. (2001) [Pubmed]
  10. The low density lipoprotein receptor-related protein modulates protease activity in the brain by mediating the cellular internalization of both neuroserpin and neuroserpin-tissue-type plasminogen activator complexes. Makarova, A., Mikhailenko, I., Bugge, T.H., List, K., Lawrence, D.A., Strickland, D.K. J. Biol. Chem. (2003) [Pubmed]
  11. Neuroserpin is post-transcriptionally regulated by thyroid hormone. Navarro-Yubero, C., Cuadrado, A., Sonderegger, P., Muñoz, A. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  12. Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin. Lebeurrier, N., Launay, S., Macrez, R., Maubert, E., Legros, H., Leclerc, A., Jamin, S.P., Picard, J.Y., Marret, S., Laudenbach, V., Berger, P., Sonderegger, P., Ali, C., di Clemente, N., Vivien, D. J. Cell. Sci. (2008) [Pubmed]
  13. Selection of neural differentiation-specific genes by comparing profiles of random differentiation. Lee, M.S., Jun, D.H., Hwang, C.I., Park, S.S., Kang, J.J., Park, H.S., Kim, J., Kim, J.H., Seo, J.S., Park, W.Y. Stem Cells (2006) [Pubmed]
 
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