Molecular bases of serpinopathies

Serpins are a protein super-family with high structural homology, involved in different physiological processes typically as serine protease inhibitors. Their structural flexibility, necessary for the inhibitory activity, makes these proteins vulnerable to point mutations, which cause the polymerisation of mutated proteins within the endoplasmic reticulum in the cell of synthesis and consequently a local damage due to polymer deposit and/or to a secretion deficit and the loss of inhibitory function. This is the origin of a class of conformational diseases, called Serpinopathies, such as alpha1-antitrypsin deficit (AATD), Hereditary Angioedema (HAE) and the Familial encephalopathy with neuroserpin inclusion bodies (FENIB), pathologies caused by mutation in the genes of alpha1-antitrypsin (AAT), C1-Inhibitor (C1-INH) and neuroserpin (NS), respectively. The research activity addresses the molecular bases of these pathologies, by studying the causes of the lack function deficit in serpins and their mechanism of polymerisation, with the aim to suggest new therapeutic strategies. The project is included in a national research initiative, the Serpin Italian Network (SIN) and it is strengthened by the participation in a European wide multidisciplinary scientific network.

Members:
Mauro Manno (Principal investigator)
Vincenzo Martorana
Samuele Raccosta