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| Content Provider | PubMed Central |
|---|---|
| Author | Saga, Giorgia Sessa, Fabio Alberto, Barbiroli Santambrogio, Carlo Russo, Rosaria Sala, Michela Raccosta, Samuele Martorana, Vincenzo Caccia, Sonia Noto, Rosina Moriconi, Claudia Miranda, Elena Rita, Grandori Manno, Mauro Bolognesi, Martino Stefano, Ricagno |
| Copyright Year | 2016 |
| Abstract | Neuroserpin (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. |
| Related Links | http://dx.doi.org/10.1038/srep18769 |
| Starting Page | 18769 |
| File Format | |
| ISSN | 20452322 |
| e-ISSN | 20452322 |
| Journal | Scientific Reports |
| Volume Number | 6 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2016-01-01 |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Science and technology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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