| Abstract | In the substantia nigra of human brain, neuromelanin (NM) released by degenerating neurons can activate microglia with consequent neurodegeneration, typical of Parkinson's disease (PD). Synthetic analogues of NM were prepared to develop a PD model reproducing the neuropathological conditions of the disease. Soluble melanin-protein conjugates were obtained by melanization of fibrillated ?-lactoglobulin (fLG). The melanic portion of the conjugates contains either eumelanic (EufLG) or mixed eumelanic/pheomelanic composition (PheofLG), the latter better simulating natural NMs. In addition, the conjugates can be loaded with controlled amounts of iron. Upon melanization, PheofLG-Fe conjugates maintain the amyloid cross-? protein core as the only structurally organized element, similarly to human NMs. The similarity in composition and structural organization with the natural pigment is reflected by the ability of synthetic NMs to activate microglia, showing potential of the novel conjugates to model NM induced neuroinflammation. Thus, synthetic NM/microglia constitute a new model to develop anti-Parkinson drugs. |
| Text | 367497 2017 10.1021/acschemneuro.6b00231 ISI Web of Science WOS 000396807900012 PubMed 28292181 neuromelanin iron amyloid fibrils synthetic melanin microglia Parkinson s disease Synthesis, Structure Characterization, and Evaluation in Microglia Cultures of Neuromelanin Analogues Suitable for Modeling Parkinson s Disease Ferrari E.; Capucciati A.; Prada I.; Zucca F.A.; D Arrigo G.; Pontiroli D.; Bridelli M.G.; Sturini M.; Bubacco L.; Monzani E.; Verderio C.; Zecca L.; Casella L. Ferrari, Emanuele; Zucca, Fabio A.; Zecca, Luigi Institute of Biomedical Technologies, National Research Council of Italy, Via Fratelli Cervi 93, 20090 Segrate Milan , Italy; Capucciati, Andrea; Sturini, Michela; Monzani, Enrico; Casella, Luigi Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy; Prada, Ilaria; D Arrigo, Giulia; Verderio, Claudia Institute of Neuroscience, National Research Council of Italy, Via Luigi Vanvitelli, 32, 20129 Milano, Italy; Pontiroli, Daniele; Bridelli, Maria G. Department of Physics and Earth Sciences M. Melloni , University of Parma, Parco Area delle Scienze 7/A, 43124 Parma, Italy; Bubacco, Luigi Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy; Verderio, Claudia IRCCS Humanitas, Via Manzoni 56, 20089 Rozzano Milan , Italy. Casella, L reprint author , Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy; e mail luigi.casella@unipv.it In the substantia nigra of human brain, neuromelanin NM released by degenerating neurons can activate microglia with consequent neurodegeneration, typical of Parkinson s disease PD . Synthetic analogues of NM were prepared to develop a PD model reproducing the neuropathological conditions of the disease. Soluble melanin protein conjugates were obtained by melanization of fibrillated lactoglobulin fLG . The melanic portion of the conjugates contains either eumelanic EufLG or mixed eumelanic/pheomelanic composition PheofLG , the latter better simulating natural NMs. In addition, the conjugates can be loaded with controlled amounts of iron. Upon melanization, PheofLG Fe conjugates maintain the amyloid cross protein core as the only structurally organized element, similarly to human NMs. The similarity in composition and structural organization with the natural pigment is reflected by the ability of synthetic NMs to activate microglia, showing potential of the novel conjugates to model NM induced neuroinflammation. Thus, synthetic NM/microglia constitute a new model to develop anti Parkinson drugs. 8 Published version Publication date 2017 Mar 15. Epub 2016 Nov 28. Articolo in rivista American Chemical Society 1948 7193 ACS chemical neuroscience ACS chemical neuroscience ACS chem. neurosci. ACS chemical neuroscience ACS Chem Neurosci American Chemical Society chemical neuroscience emanuele.ferrari FERRARI EMANUELE PRADA ILARIA luigi.zecca ZECCA LUIGI D ARRIGO GIULIA claudia.verderio VERDERIO CLAUDIA fabioandrea.zucca ZUCCA FABIO ANDREA |
