Neuroserpin Explained

Neuroserpin is a protein that in humans is encoded by the SERPINI1 gene.^[1]

It is associated with Familial encephalopathy with neuroserpin inclusion bodies.

Serine protease inhibitors of the serpin superfamily are involved in many cellular processes. Neuroserpin was first identified as a protein secreted from the axons of dorsal root ganglion neurons (Stoeckli et al., 1989). It is expressed in the late stages of neurogenesis during the process of synapse formation.[supplied by OMIM]^[1]

Interactions

SERPINI1 has been shown to interact with Tissue plasminogen activator.^[2]

Further reading

• Yepes M . Lawrence DA . Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. . Thromb. Haemost. . 91 . 3 . 457–64 . 2004 . 14983220 . 10.1160/TH03-12-0766 . 39118265 .
• Schrimpf SP, Bleiker AJ, Brecevic L, etal . Human neuroserpin (PI12): cDNA cloning and chromosomal localization to 3q26. . Genomics . 40 . 1 . 55–62 . 1997 . 9070919 . 10.1006/geno.1996.4514 .
• Hastings GA, Coleman TA, Haudenschild CC, etal . Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival. . J. Biol. Chem. . 272 . 52 . 33062–7 . 1998 . 9407089 . 10.1074/jbc.272.52.33062 . free .
• Davis RL, Shrimpton AE, Holohan PD, etal . Familial dementia caused by polymerization of mutant neuroserpin. . Nature . 401 . 6751 . 376–9 . 1999 . 10517635 . 10.1038/43894 . 4413322 . free .
• Chang WS, Chang NT, Lin SC, etal . Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26. . Genes Chromosomes Cancer . 29 . 3 . 240–55 . 2000 . 10992299 . 10.1002/1098-2264(2000)9999:9999<::AID-GCC1029>3.0.CO;2-A . 23441111 .
• Belorgey D . Crowther DC . Mahadeva R . Lomas DA . Mutant Neuroserpin (S49P) that causes familial encephalopathy with neuroserpin inclusion bodies is a poor proteinase inhibitor and readily forms polymers in vitro. . J. Biol. Chem. . 277 . 19 . 17367–73 . 2002 . 11880376 . 10.1074/jbc.M200680200 . free .
• Davis RL, Shrimpton AE, Carrell RW, etal . Association between conformational mutations in neuroserpin and onset and severity of dementia. . Lancet . 359 . 9325 . 2242–7 . 2002 . 12103288 . 10.1016/S0140-6736(02)09293-0 . 10722760 .
• Barker-Carlson K . Lawrence DA . Schwartz BS . Acyl-enzyme complexes between tissue-type plasminogen activator and neuroserpin are short-lived in vitro. . J. Biol. Chem. . 277 . 49 . 46852–7 . 2003 . 12228252 . 10.1074/jbc.M207740200 . free .
• Parmar PK, Coates LC, Pearson JF, etal . Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cells. . J. Neurochem. . 82 . 6 . 1406–15 . 2002 . 12354288 . 10.1046/j.1471-4159.2002.01100.x . 23571680 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Miranda E . Römisch K . Lomas DA . Mutants of neuroserpin that cause dementia accumulate as polymers within the endoplasmic reticulum. . J. Biol. Chem. . 279 . 27 . 28283–91 . 2004 . 15090543 . 10.1074/jbc.M313166200 . free .
• Teesalu T, Kulla A, Simisker A, etal . Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system. . Thromb. Haemost. . 92 . 2 . 358–68 . 2005 . 15269833 . 10.1160/TH02-12-0310 .
• Belorgey D, Sharp LK, Crowther DC, etal . Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers: implications for the epilepsy seen in the dementia FENIB. . Eur. J. Biochem. . 271 . 16 . 3360–7 . 2004 . 15291813 . 10.1111/j.1432-1033.2004.04270.x .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Onda M . Belorgey D . Sharp LK . Lomas DA . Latent S49P neuroserpin forms polymers in the dementia familial encephalopathy with neuroserpin inclusion bodies. . J. Biol. Chem. . 280 . 14 . 13735–41 . 2005 . 15664988 . 10.1074/jbc.M413282200 . free .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Kinghorn KJ, Crowther DC, Sharp LK, etal . Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease. . J. Biol. Chem. . 281 . 39 . 29268–77 . 2006 . 16849336 . 10.1074/jbc.M600690200 . free .
• Chen PY, Chang WS, Chou RH, etal . Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner. . BMC Mol. Biol. . 8 . 2 . 2007 . 17212813 . 10.1186/1471-2199-8-2 . 1796892 . free .
• Gourfinkel-An I, Duyckaerts C, Camuzat A, etal . Clinical and neuropathologic study of a French family with a mutation in the neuroserpin gene. . Neurology . 69 . 1 . 79–83 . 2007 . 17606885 . 10.1212/01.wnl.0000265052.99144.b5 . 39704442 .

External links

• The MEROPS online database for peptidases and their inhibitors: I04.025

Notes and References

1. Web site: Entrez Gene: SERPINI1 serpin peptidase inhibitor, clade I (neuroserpin), member 1.
2. Parmar . Parmjeet K . Coates Leigh C . Pearson John F . Hill Rena M . Birch Nigel P . September 2002 . Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cells . J. Neurochem. . 82 . 6 . 1406–15 . 0022-3042. 12354288 . 10.1046/j.1471-4159.2002.01100.x . 23571680 .