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)
Impact factor
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