Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Naples, Italy.
Curr Med Chem. 2011;18(12):1832-45. doi: 10.2174/092986711795496863.
Aberrant oxidative pathways of catecholamine neurotransmitters, i.e. dopamine and norepinephrine, are an important biochemical correlate of catecholaminergic neuron loss in some disabling neurodegenerative diseases of the elderly, notably Parkinson's disease. In an oxidative stress setting, under conditions of elevated lipid peroxidation, iron accumulation, impaired mitochondrial functioning and antioxidant depletion, catecholamines are oxidatively converted to the corresponding o-quinones, which may initiate a cascade of spontaneous reactions, including intramolecular cyclization, aminoethyl side chain fission and interaction with molecular targets. The overall outcome of the competing pathways may vary depending on contingent factors and the biochemical environment, and may include formation of nitrated derivatives, neuromelanin deposition, generation of chain fission products, conjugation with L-cysteine leading eventually to cytotoxic responses and altered cellular function. In addition, catecholamines may interact with products of lipid peroxidation and other species derived from oxidative breakdown of biomolecules, notably glyoxal and other aldehydes, leading e.g. to tetrahydroisoquinolines via Pictet-Spengler chemistry. After a brief introductory remark on oxidative stress biochemistry, the bulk of this review will deal with an overview of the basic chemical pathways of catecholamine oxidation, with special emphasis on the analogies and differences between the central neurotransmitters dopamine and norepinephrine. This chemistry will form the basis for a concise discussion of the latest advances in the mechanisms of catecholamine-associated neurotoxicity in neuronal degeneration.
儿茶酚胺神经递质（即多巴胺和去甲肾上腺素）的异常氧化途径是某些老年人致残性神经退行性疾病（尤其是帕金森病）中儿茶酚胺能神经元丧失的重要生化相关性。在氧化应激环境下，在脂质过氧化、铁积累、线粒体功能障碍和抗氧化剂耗竭升高的情况下，儿茶酚胺被氧化转化为相应的邻醌，这可能引发一系列自发反应，包括分子内环化、氨基乙基侧链断裂和与分子靶标相互作用。竞争途径的总体结果可能因偶然因素和生化环境而异，并且可能包括形成硝化衍生物、神经黑色素沉积、产生链断裂产物、与 L-半胱氨酸结合，最终导致细胞毒性反应和改变细胞功能。此外，儿茶酚胺可能与脂质过氧化产物和其他源自生物分子氧化分解的物质相互作用，特别是通过丙二醛和其他醛，通过 Pictet-Spengler 化学生成四氢异喹啉。在简要介绍氧化应激生物化学之后，本综述的大部分内容将概述儿茶酚胺氧化的基本化学途径，特别强调中枢神经递质多巴胺和去甲肾上腺素之间的相似性和差异。这种化学将为简明讨论神经元退行性变中儿茶酚胺相关神经毒性的机制的最新进展提供基础。
