New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals
New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals
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DOI：
10.1073/pnas.0808768105
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发表时间：
2008-11-11
影响因子：
11.1
通讯作者：
Zucca, Fabio A.
中科院分区：
文献类型：
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作者：
Zecca, Luigi;Bellei, Chiara;Zucca, Fabio A.
黑色素型的神经元色素在壳核、皮质、小脑和人脑的其他主要区域中被鉴定。这些色素由大小为30 nm的颗粒组成，与脂滴一起包含在细胞器中，并且它们在衰老过程中积累，在主要脑区域中达到高达1.5-2.6 μ g/mg组织的浓度。这些色素，我们称之为神经黑素，含有黑素、脂质和肽成分。黑素组分在结构上是芳香族的，含有稳定的自由基，并且由前体分子半胱氨酰-3，4-二羟基苯丙氨酸合成。这与黑质的神经黑色素形成对比，黑色素前体是半胱氨酰多巴胺。这些神经元色素与皮肤中的黑色素有一些结构相似性。神经黑素的脂质成分的前体是存在于周围细胞器中的多不饱和脂质。神经黑素在人脑不同区域的合成是一个重要的保护过程，因为黑素成分是通过去除反应性/毒性醌类产生的，否则会导致神经毒性。此外，所得到的黑色素组分通过其螯合和积累金属（包括汞和铅等对环境有毒的金属）的能力而起到额外的保护作用。
Neuronal pigments of melanic type were identified in the putamen, cortex, cerebellum, and other major regions of human brain. These pigments consist of granules 30 nm in size, contained in organelles together with lipid droplets, and they accumulate in aging, reaching concentrations as high as 1.5-2.6 mu g/mg tissue in major brain regions. These pigments, which we term neuromelanins, contain melanic, lipid, and peptide components. The melanic component is aromatic in structure, contains a stable free radical, and is synthesized from the precursor molecule cysteinyl-3,4-dihydroxyphenylalanine. This contrasts with neuromelanin of the substantia nigra, where the melanic precursor is cysteinyl-dopamine. These neuronal pigments have some structural similarities to the melanin found in skin. The precursors of lipid components of the neuromelanins are the polyunsaturated lipids present in the surrounding organelles. The synthesis of neuromelanins in the various regions of the human brain is an important protective process because the melanic component is generated through the removal of reactive/toxic quinones that would otherwise cause neurotoxicity. Furthermore, the resulting melanic component serves an additional protective role through its ability to chelate and accumulate metals, including environmentally toxic metals such as mercury and lead.