The binding of neuromelanin (NM) to iron is of interest due to its role in brain aging and Parkinson's disease. In the present work, infrared spectra of both NM isolated from human brain and of synthetic NM analogues are reported with the aim of identifying the main functional groups and their chelating ability for iron. It is observed that a peptide and an aliphatic chain are present in the NM structure. The coordination of iron in NM occurs through^OH phenolic units. In synthetic melanin samples, the preferred sites for iron binding are^OH phenolic and T TNH indolic groups. Amino acid analysis confirmed the presence of a peptide component in NM and synthetic melanin incubated in putamen homogenate. In addition, the elemental analysis demonstrated the presence of an aliphatic component specific of NM.z 1999 Federation of European Biochemical Societies.

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 β-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-β 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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Although water is a structural and functional determinant in melanins, a direct study of the interaction between water and melanin is still lacking and is the subject of the present work. Melanin forms in cells and organisms' colloidal particles deriving from the hierarchical aggregation of smaller subunits such as protomolecules, stacking units, and small aggregates: its functions must be interpreted in terms of solid-state and surface properties. They are strictly connected to the porosity of the particles when they interact with water and other chemicals. The structural characteristics of water sorbed in the pores are investigated by means of FTIR in the OH stretching vibration region (4000-3000 cm(-1)) on Sepia and synthetic l-Dopa melanins at different and controlled hydration degrees (a(w) = 0.06 to 0.92). Three distinct component bands are recognized in the main OH stretching band, corresponding to three distinct water populations, showing differing behavior for the two kinds of melanin and thus accounting for different molecular structures. On this basis, the historical, albeit current, model of hydration structure of melanin granules, a "strongly" and a "weakly" bound fraction, is reassessed and rediscussed.