Synthesis, Structure Characterization, and Evaluation in Microglia Cultures of Neuromelanin Analogues Suitable for Modeling Parkinson's Disease.
Emanuele FerrariAndrea CapucciatiIlaria PradaFabio Andrea ZuccaGiulia D'ArrigoDaniele PontiroliMaria Grazia BridelliMichela SturiniLuigi BubaccoEnrico MonzaniClaudia VerderioLuigi ZeccaLuigi CasellaPublished in: ACS chemical neuroscience (2016)
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.
Keyphrases
- cancer therapy
- inflammatory response
- photodynamic therapy
- neuropathic pain
- drug delivery
- spinal cord
- molecular docking
- lipopolysaccharide induced
- traumatic brain injury
- lps induced
- amino acid
- drug induced
- small molecule
- protein protein
- wound healing
- climate change
- cerebral ischemia
- subarachnoid hemorrhage
- brain injury
- stress induced