Synthesis, Structure Characterization, and Evaluation in Microglia Cultures of Neuromelanin Analogues Suitable for Modeling Parkinson’s Disease

Ferrari, Emanuele; Capucciati, Andrea; Prada, Ilaria; Zucca, Fabio A.; D’Arrigo, Giulia; Pontiroli, Daniele; Bridelli, Maria Grazia; Sturini, Michela; Bubacco, Luigi; Monzani, Enrico; Verderio, Claudia; Zecca, Luigi; Casella, Luigi

doi:10.1021/acschemneuro.6b00231

Cited by 36 publications

(68 citation statements)

References 60 publications

(155 reference statements)

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“…[24] There is no evidence for the involvement of enzymatic reactions in the DA oxidation process to NM, and tyrosinase,r esponsible for the formation of peripheral melanins, [156] was not found in aproteomic analysis of NM. [158] Thepresence of an amyloid protein/peptide core in NM is confirmed by Xray diffraction studies of the NM pigments extracted from several brain areas;t hese studies invariably show the characteristic pattern of 4.7 typical of cross-b structure, related to the distance between b chains in the protein backbone. Thei nitial melanin-protein conjugate is further elaborated by attachment of lipid components and sequestered within specialized cytoplasmic NM autophagic-lysosomal organelles surrounded by ad ouble membrane.…”

Section: Dopamine In Neuromelanin Biosynthesismentioning

confidence: 83%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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Dopamine (DA) is the most important catecholamine in the brain, as it is the most abundant and the precursor of other neurotransmitters. Degeneration of nigrostriatal neurons of substantia nigra pars compacta in Parkinson's disease represents the best‐studied link between DA neurotransmission and neuropathology. Catecholamines are reactive molecules that are handled through complex control and transport systems. Under normal conditions, small amounts of cytosolic DA are converted to neuromelanin in a stepwise process involving melanization of peptides and proteins. However, excessive cytosolic or extraneuronal DA can give rise to nonselective protein modifications. These reactions involve DA oxidation to quinone species and depend on the presence of redox‐active transition metal ions such as iron and copper. Other oxidized DA metabolites likely participate in post‐translational protein modification. Thus, protein–quinone modification is a heterogeneous process involving multiple DA‐derived residues that produce structural and conformational changes of proteins and can lead to aggregation and inactivation of the modified proteins.

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Section: Dopamine In Neuromelanin Biosynthesismentioning

confidence: 83%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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“…Our results do suggest that, depending on the intensity of the oxidative reaction, chemically-distinct, dark-or light-colored MN-like pigments could be generated depending on the type of precursor that is present. Such physically and chemically distinct MN materials could find different applications 7,16,[43][44][45][46] or possess different cell-biological properties [47][48][49][50][51][52] In addition, our results suggest that the absence of a dark color does not necessarily mean the absence of MN-like materials which may have implications for the evaluation of histological or fossil specimens. [53][54] …”

Section: 323uv-vis Spectroscopy and Fluorescence Emissionmentioning

confidence: 90%

Dark- or Light-Colored Melanins: Generating Pigments Using Fe2+ and H2O2

Vercruysse

Russell²,

Knight³

et al. 2017

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We have studied the formation of melanin-like pigments from catechol or pyrogallol and a wide range of other phenolic compounds using Fe 2+ and H 2 O 2 . Combining UV_Vis spectroscopic measurements and size-exclusion chromatography analyses we evaluated the impact of the intensity of the oxidation reaction by varying the concentration of H 2 O 2 present in the reaction mixtures. All compounds tested, except tyrosine, reacted readily leading to mixtures that were black, brown or yellow-orange in color. For many compounds tested, the use of increasing concentrations of H 2 O 2 resulted in either precipitation of the pigment or the formation of a soluble, lighter-colored pigment. With catechol or pyrogallol as model compounds, and using different concentrations of H 2 O 2 , several materials were synthesized, purified and dried. The physic-chemical properties of these materials were compared to the properties of melanin-like pigments synthesized from the same precursors using air-oxidation in an alkaline environment. For both precursors, a distinct chemical change, as judged from FT-IR spectroscopy, was introduced in the melanin structures when using H 2 O 2 as the oxidizing agent and the relative intensity of this distinct signal strengthened with increasing concentration of H 2 O 2 used in the reaction. In general, our results suggest that depending on the precursor molecule and the intensity of the oxidizing reaction conditions involved, light-or dark-colored melanin-like pigments can be generated. This may be an important factor when evaluating the visible outlook of histological or archeological specimens: the presence of a lighter color or the absence of a dark color may not necessarily mean the absence of melanin-like biomolecules.

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“…[49][50] Our observation that the various L-DOPA-based MN materials are capable of inducing IL-1 or IL-6 release from immune cells (see Figure 4) is in accordance with our previous observations and other reports. [19][20][21]23 Despite their differences in mode of synthesis, PS-mediated, base-mediated or Fe 2+ /H 2 O 2 -mediated oxidation, all L-DOPA-based materials we have evaluated thus far appeared to enhance the ILrelease from immune cells. Thus, this biological effect may not be majorly impacted by the physicchemical differences that exist between these different materials.…”

Section: Discussionmentioning

confidence: 99%

Light- or Dark-Colored, L-DOPA-Based Melanins

Vercruysse¹,

Whalen²

2018

Preprint

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This report is a continuation of previous research on the H 2 O 2 -mediated synthesis of melanin-like pigments. We synthesized and characterized L-DOPA-based pigments using air-or H 2 O 2 -mediated oxidation. We compared their physic-chemical properties and evaluated their capacity to affect the interleukin release from immune cells. The use of higher concentrations of H 2 O 2 resulted in melanin-like materials with a distinct chemical signature in their FT-IR spectra and a lighter color. All pigments enhanced the interleukin release from immune cells. The possibility that lighter-colored melanins can be generated is discussed in the context of the importance of melanin-based pigmentation in human physiology.

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Synthesis, Structure Characterization, and Evaluation in Microglia Cultures of Neuromelanin Analogues Suitable for Modeling Parkinson’s Disease

Cited by 36 publications

References 60 publications

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Dark- or Light-Colored Melanins: Generating Pigments Using Fe2+ and H2O2

Light- or Dark-Colored, L-DOPA-Based Melanins

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