Anno2016
AutoriSaga, Giorgia; Sessa, Fabio; Barbiroli, Alberto; Santambrogio, Carlo; Russo, Rosaria; Sala, Michela; Raccosta, Samuele; Martorana, Vincenzo; Caccia, Sonia; Noto, Rosina; Moriconi, Claudia; Miranda, Elena; Grandori, Rita; Manno, Mauro; Bolognesi, Martino;
AbstractNeuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain.
RivistaScientific Reports (nature Publishing Group)
ISSN2045-2322
Impact factor
Volume6
Pagina inizio18769-1
Pagina fine18769-12
Autori IBFMauro MANNO, Vincenzo MARTORANA, Rosina NOTO, Samuele RACCOSTA, Martino BOLOGNESI
Linee di Ricerca IBFMD.P01.002.001, MD.P01.005.001
Sedi IBFIBF.MI, IBF.PA