The neuromelanin of the human substantia nigra

Carstam, R; Brinck, Carita; Hindemith-Augustsson, A.; Rorsman, H; Rosengren, E.

doi:10.1016/0925-4439(91)90100-n

Cited by 146 publications

(123 citation statements)

References 25 publications

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“…Thus, benzothiazine and indole units are found in this polymer [61][62][63][64][65]. According to Bush et al [53], neuromelanin granules should have pheomelanin in the core and eumelanin in the surface, which is compatible with an occasional exhaustion of the glutathione or cysteine reduction system during neuromelanin formation [61].…”

Section: Animal Melaninsmentioning

confidence: 88%

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

Solano

2014

New Journal of Science

429

462

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This review presents a general view of all types of melanin in all types of organisms. Melanin is frequently considered just an animal cutaneous pigment and is treated separately from similar fungal or bacterial pigments. Similarities concerning the phenol precursors and common patterns in the formation routes are discussed. All melanins are formed in a first enzymatically-controlled phase, generally a phenolase, and a second phase characterized by an uncontrolled polymerization of the oxidized intermediates. In that second phase, quinones derived from phenol oxidation play a crucial role. Concerning functions, all melanins show a common feature, a protective role, but they are not merely photoprotective pigments against UV sunlight. In pathogenic microorganisms, melanization becomes a virulence factor since melanin protects microbial cells from defense mechanisms in the infected host. In turn, some melanins are formed in tissues where sunlight radiation is not a potential threat. Then, their redox, metal chelating, or free radical scavenging properties are more important than light absorption capacity. These pigments sometimes behave as a doubleedged sword, and inhibition of melanogenesis is desirable in different cells. Melanin biochemistry is an active field of research from dermatological, biomedical, cosmetical, and microbiological points of view, as well as fruit technology.

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Section: Animal Melaninsmentioning

confidence: 88%

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

Solano

2014

New Journal of Science

429

462

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“…To illustrate, formation of DHBT-1 requires only DA and CySH together in an oxidizing environment (Zhang and Dryhurst, 1994;Shen and Dryhurst, 1996). The neuromelanin that normally pigments SN dopaminergic cells provides unequivocal evidence that an oxidizing environment exists in the cytoplasm of these neurons, that DA is oxidized, and that during the deposition of the black polymer little or no CySH or GSH is available (Slivka et al, 1987;Carstam et al, 1991;Zhang and Dryhurst, 1994;Shen and Dryhurst, 1996). Some evidence suggests that human SN neuromelanin is a copolymer formed by oxidation of DA and 5-S-CyS-DA (Carstam et al, 1991;Odh et al, 1994), although other studies have found no evidence for residues derived from the latter cysteinyl conjugate (Wakamatsu et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Together, these observations suggest that SN neurons having high basal levels of DA oxidation are predisposed to degeneration in PD and, furthermore, that the fundamental mechanisms underlying the degenerative processes divert or even block the neuromelanin pathway. It may be of significance, therefore, that in vitro CySH and GSH divert the oxidation of DA to black indolic melanin polymer by scavenging DA-o-quinone to form, initially, soluble cysteinyl or glutathionyl conjugates of the neurotransmitter, respectively (Carstam et al, 1991;Dryhurst, 1994, 1995;Shen and Dryhurst, 1996).…”

mentioning

confidence: 99%

Irreversible Inhibition of Mitochondrial Complex I by 7‐(2‐Aminoethyl)‐3,4‐Dihydro‐5‐Hydroxy‐2H‐1,4‐Benzothiazine‐3‐Carboxylic Acid (DHBT‐1): A Putative Nigral Endotoxin of Relevance to Parkinson's Disease

Dryhurst

1997

Journal of Neurochemistry

118

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Based on a number of lines of evidence, we have proposed recently that a very early step in the pathogenesis of idiopathic Parkinson's disease might be elevated translocation of L-cysteine into neuromelanin-pigmented dopaminergic cell bodies in the substantia nigra. In vitro studies suggest that such an influx of L-cysteine would divert the neuromelanin pathway by scavenging dopamine-o-quinone, the proximate autoxidation product of dopamine, to give 5-S-cysteinyldopamine, which is oxidized further to 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1 ‚4-benzothiazine-3-carboxylic acid (DHBT-1) and other cysteinyldopamines and dihydrobenzothiazines. In this study, it is demonstrated that DHBT-1 inhibits ADP-stimulated oxidation of malate and pyruvate (state 3 or complex I respiration) when incubated with intact rat brain mitochondria with an IC 50 of '-'0.80 mM. Incubation of DHBT-1 with freeze-thawed rat brain mitochondria in both the presence and absence of KCN and! or NADH causes an irreversible, time-dependent decrease of NADH-coenzyme Q1 reductase activity. Significantly lower concentrations of DHBT-1 are necessary to cause this effect when mitochondrial membranes are incubated in the absence of KCN and NADH. The irreversible inhibition of mitochondrial complex I caused by DHBT-1 under the latter conditions could be blocked only partially by glutathione, ascorbic acid, superoxide dismutase, or catalase. Together, these results suggest that DHBT-1 can cross the outer mitochondrial membrane and irreversibly inhibit complex I by a mechanism that is not primarily related to oxygen radical-mediated damage. Formation of DHBT-1 requires only dopamine, L-cysteine, and an oxidizing environment, conditions that may well exist in the cytoplasm of neuromelanin-pigmented dopaminergic neurons in the parkinsonian substantia nigra.

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“…It seems that this biopolimer may be actively involved in neurodegenerative processes that occur during natural ageing and Parkinson's disease [1]. Numerous data indicate that the nigral pigment consists of indole-type (eumelanin) and benzothiazine-type (pheomelanin) subunits, derived oxidatively from dopamine and 5-S-cysteinyldopamine, respectively [2,3]. EPR studies evidenced that both structural constituents of natural neuromelanin are the sources of distinct kind of stable organic radicals [4].…”

Section: Introductionmentioning

confidence: 99%

EPR Investigations of Model Neuromelanins

2000

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The aim of this work was to compare free radical properties of some model neuromelanins obtained from dopamine and its mixture with 5-S-cysteinyldopamine in various molar ratios. The EPR method was used in these investigations; the samples were detected at X and K bands. The parameters of EPR spectra, free radicals concentrations in air and in vacuum, the influence of microwave power and temperature on intensity of resonance signals were measured.

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The neuromelanin of the human substantia nigra

Cited by 146 publications

References 25 publications

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

Irreversible Inhibition of Mitochondrial Complex I by 7‐(2‐Aminoethyl)‐3,4‐Dihydro‐5‐Hydroxy‐2H‐1,4‐Benzothiazine‐3‐Carboxylic Acid (DHBT‐1): A Putative Nigral Endotoxin of Relevance to Parkinson's Disease

EPR Investigations of Model Neuromelanins

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