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Sökning: WFRF:(Possenti Andrea)

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1.
  • Watts, Anna L., et al. (författare)
  • Dense matter with eXTP
  • 2019
  • Ingår i: Science China Physics, Mechanics & Astronomy. - : Science Press. - 1674-7348 .- 1869-1927. ; 62:2
  • Forskningsöversikt (refereegranskat)abstract
    • In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Sciences, the eXTP mission is expected to be launched in the mid 2020s.
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2.
  • Chia, Sean, et al. (författare)
  • A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions
  • Ingår i: ACS Chemical Neuroscience. - 1948-7193.
  • Tidskriftsartikel (refereegranskat)abstract
    • Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer’s disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al3+, Cu2+, Fe2+, and Zn2+) and show that they differ in their structure and toxicity in human neuroblastoma cells. We then describe a correlation between the size of the oligomers and their neurotoxic activity, which provides a type of structure-toxicity relationship for these Aβ40 oligomer species. These results provide insight into the possible role of metal ions in Alzheimer’s disease by the stabilization of Aβ oligomers.
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3.
  • Chia, Sean, et al. (författare)
  • Structure-Based Discovery of Small-Molecule Inhibitors of the Autocatalytic Proliferation of α-Synuclein Aggregates
  • 2023
  • Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 20:1, s. 183-193
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of amyloid fibrils of α-synuclein is closely associated with Parkinson's disease and related synucleinopathies. It is still very challenging, however, to systematically discover small molecules that prevent the formation of these aberrant aggregates. Here, we describe a structure-based approach to identify small molecules that specifically inhibit the surface-catalyzed secondary nucleation step in the aggregation of α-synuclein by binding to the surface of the amyloid fibrils. The resulting small molecules are screened using a range of kinetic and thermodynamic assays for their ability to bind α-synuclein fibrils and prevent the further generation of α-synuclein oligomers. This study demonstrates that the combination of structure-based and kinetic-based drug discovery methods can lead to the identification of small molecules that selectively inhibit the autocatalytic proliferation of α-synuclein aggregates.
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