Abstract
Our current knowledge about the cellular mechanisms underlying serpin-related disorders, the serpinopathies, is predominantly based on studies in cell culture models of disease, particularly for alpha-1 antitrypsin (AAT, SERPINA1) deficiency causing emphysema and the familial encephalopathy with neuroserpin (NS, SERPINI1) inclusion bodies (FENIB). FENIB, a neurodegenerative dementia, is caused by polymerization of NS (Miranda and Lomas, Cell Mol Life Sci 63:709–722, 2006; Roussel BD et al., Epileptic Disor 18:103–110, 2016), while AAT deficiency presents as a result of several divergent mutations in the AAT gene that cause lack of protein synthesis or complete intracellular degradation (null variants) or polymer formation (polymerogenic variants) (Lomas et al., J Hepatol 65:413–424, 2016; Greene et al., Nat Rev Dis Primers 2:16051, 2016; Ferrarotti et al. Orphanet J Rare D 9:172, 2014). Both diseases have been extensively modeled in cell culture systems by expressing mutant variants in a variety of ways. Here we describe the methodologies we follow in our cell model systems used to examine serpin disorders.
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Acknowledgments
We thank Romina Berardelli for technical assistance. This work was supported in part by Fondazione Cariplo (#2013-0967) to A.F. and by Sapienza Research grant 2016 (Sapienza University of Rome, Italy) to E.M.
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Fra, A., D’Acunto, E., Laffranchi, M., Miranda, E. (2018). Cellular Models for the Serpinopathies. In: Lucas, A. (eds) Serpins. Methods in Molecular Biology, vol 1826. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8645-3_7
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DOI: https://doi.org/10.1007/978-1-4939-8645-3_7
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