0000000000974589
AUTHOR
M Bolognesi
On the molecular structure of human neuroserpin polymers. Coagulation, fragmentation and latentization control serpin aggregation
The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85 °C, display the same isosbestic points in the Amide I band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45 °C suggesting that the polymerization rate limiting step is the formation of an activated monomeric species. The polymer structure…
Inactivation and polymerization of human neuroserpin
Neuroserpin is an inhibitory enzyme, belonging to the family of serpins and involved in several pathologies, such as ischemia, Alzheimer disease, and FENIB (Familial Encephalopathy with Neuroserpin Inclusion Body). Here, we study the mechanism of neuroserpin inactivation and polymerization by different experimental techniques (static and dynamic light scattering, liquid chromatography, Fourier transform infrared spectroscopy, emission spectroscopy). Our results show that at intermediate temperatures (45-55 °C) neuroserpin forms flexible polymers with a size from a few tens to a few hundreds of nanometers. At high temperatures, above 80 °C, our results reveal a different polymeric form, reac…
The beam and detector of the NA62 experiment at CERN
NA62 is a fixed-target experiment at the CERN SPS dedicated to measurements of rare kaon decays. Such measurements, like the branching fraction of the $K^{+} \rightarrow \pi^{+} \nu \bar\nu$ decay, have the potential to bring significant insights into new physics processes when comparison is made with precise theoretical predictions. For this purpose, innovative techniques have been developed, in particular, in the domain of low-mass tracking devices. Detector construction spanned several years from 2009 to 2014. The collaboration started detector commissioning in 2014 and will collect data until the end of 2018. The beam line and detector components are described together with their early …
Functional and dysfunctional isoforms of human neuroserpin
Neuroserpin (NS) is a serine protease inhibitor (SERPIN) involved in different neurological pathologies, including the Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), related to the aberrant polymerization of NS mutants. Here we present an in vitro and in silico characterization of native NS and its dysfunctional conformation isoforms: the proteolytically cleaved conformer, the inactive latent conformer, and the polymeric conformer. Using circular dichroism and fluorescence spectroscopy, we present an experimental validation of the latent model and highlight the main structural features of the different conformers. In par- ticular, emission spectra of aromatic residues yi…