Journal
ACS CHEMICAL NEUROSCIENCE
Volume 8, Issue 3, Pages 501-512Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.6b00231
Keywords
Neuromelanin; iron; amyloid fibrils; synthetic melanin; microglia; Parkinson's disease
Funding
- Italian Ministry of Education, University, and Research (MIUR) - Research Projects of National Interest (PRIN) [2015T778JW]
- Fondazione Umberto Veronesi Fellowship
- MIUR - National Research Programme (PNR) - CNR Flagship InterOmics Project [PB.P05]
- PNR - CNR Aging program
- Lombardy Region - CNR, Framework Agreement, MbMM Project [18089/RCC]
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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 ss-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-ss 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.
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