Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, xenobiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and neurodegeneration related to its capabilities as an antioxidant and scavenging of harmful molecules, versus its involvement in oxidative stress and aberrant immune response, depending on NM saturation state and its extracellular release.

中文翻译：

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神经黑色素悖论及其在氧化应激和神经变性中的双重作用

衰老与关键的脑稳态机制的功能障碍增加有关，并且是大多数神经退行性疾病的主要危险因素。然而，失调的程度和特定途径的影响将正常衰老与神经退行性疾病分开。特别地，儿茶酚胺能神经递质的神经元代谢似乎是受不同神经变性影响的特异性敏感途径。在人类中，儿茶酚胺能性神经元的特征是与年龄相关的神经黑色素（NM）积累，使神经元的躯体变黑。这种细胞内NM似乎是有毒分子的非常有效的淬灭剂。但是，当神经元退化时，NM及其负载（许多未降解的细胞成分，过渡金属，脂质，异源生物）有助于引发和恶化最终的免疫反应，加剧氧化应激，最终导致神经退行性过程。这篇综述着重分析了NM在正常衰老和神经变性中的作用，这与NM作为抗氧化剂和清除有害分子的能力有关，而取决于NM饱和状态及其细胞外释放，NM参与氧化应激和异常的免疫反应。