Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs (Articolo in rivista)

Type
Label
  • Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pone.0009234 (literal)
Alternative label
  • Latawiec, Diane; Herrera, Fernando; Bek, Alpan; Losasso, Valeria; Candotti, Michela; Benetti, Federico; Carlino, Elvio; Kranjc, Agata; Lazzarino, Marco; Gustincich, Stefano; Carloni, Paolo; Legname, Giuseppe (2010)
    Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Latawiec, Diane; Herrera, Fernando; Bek, Alpan; Losasso, Valeria; Candotti, Michela; Benetti, Federico; Carlino, Elvio; Kranjc, Agata; Lazzarino, Marco; Gustincich, Stefano; Carloni, Paolo; Legname, Giuseppe (literal)
Pagina inizio
  • e9234 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 5 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Scuola Int Super Studi Avanzati, Scuola Int Super Studi Avanzati, Dept Neurobiol, Trieste, Italy 2. Scuola Int Super Studi Avanzati, Scuola Int Super Studi Avanzati, Dept Stat & Biol Phys, Trieste, Italy 3. Italian Inst Technol, SISSA Unit, Trieste, Italy 4. Ctr Mol Biomed CBM Scrl, Consorzio Ctr Biomed Mol, Trieste, Italy 5. TASC INFM Natl Lab, Trieste, Italy 6. Sincrotrone Trieste SCpA, ELETTRA Lab, Trieste, Italy (literal)
Titolo
  • Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs (literal)
Abstract
  • The action of dopamine on the aggregation of the unstructured alpha-synuclein (alpha-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit alpha-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of alpha-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to alpha-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. (literal)
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