Department of Pharmacology, University of Göteborg (at the time of the study), Göteborg, Sweden.
J Neural Transm (Vienna). 2024 Mar;131(3):213-228. doi: 10.1007/s00702-023-02718-2. Epub 2024 Jan 18.
The present study was performed to examine if catechol oxidation is higher in brains from patients with Parkinson's disease compared to age-matched controls, and if catechol oxidation increases with age. Brain tissue from Parkinson patients and age-matched controls was examined for oxidation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) to corresponding quinones, by measurement of 5-S-cysteinyl-dopamine, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA. The cysteinyl catechols are assumed to be biomarkers for DA, DOPAC and DOPA autoxidation and part of the biosynthetic pathway of neuromelanin. The concentrations of the 5-S-cysteinyl catechols were lower, whereas the 5-S-cysteinyl-DA/DA and 5-S-cysteinyl-DOPAC/DOPAC ratios tended to be higher in the Parkinson group compared to controls, which was interpreted as a higher degree of oxidation. High 5-S-cysteinyl-DA/DA ratios were found in the substantia nigra of a sub-population of the Parkinson group. Based on 5-S-cysteinyl-DA/DA ratios, dopamine oxidation was found to increase statistically significantly with age in the caudate nucleus, and non-significantly in the substantia nigra. In conclusion, the occurrence of 5-S-cysteinyl-DA, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA was demonstrated in dopaminergic brain areas of humans, a tendency for higher oxidation of DA in the Parkinson group compared to controls was observed as well as a statistically significant increase in DA oxidation with age. Possibly, autoxidation of DA and other catechols are involved in both normal and pathological ageing of the brain. This study confirms one earlier but small study, as well as complements one study on non-PD cases and one study on both PD cases and controls on NM bound or integrated markers or catechols.
本研究旨在检测帕金森病患者脑中儿茶酚氧化是否高于年龄匹配的对照组，以及儿茶酚氧化是否随年龄增加而增加。通过测量 5-S-半胱氨酸-DOPA、5-S-半胱氨酸-DOPAC 和 5-S-半胱氨酸-DOPA 来检测多巴胺、3,4-二羟基苯乙酸 (DOPAC) 和 3,4-二羟基苯丙氨酸 (DOPA) 氧化为相应的醌，检查帕金森病患者和年龄匹配的对照组的脑组织中儿茶酚氧化情况。半胱氨酸儿茶酚被认为是 DA、DOPAC 和 DOPA 自动氧化的生物标志物，也是神经黑色素生物合成途径的一部分。与对照组相比，帕金森病组的 5-S-半胱氨酸儿茶酚浓度较低，而 5-S-半胱氨酸-DA/DA 和 5-S-半胱氨酸-DOPAC/DOPAC 比值趋于较高，这被解释为氧化程度较高。在帕金森病组的一个亚群的黑质中发现了高 5-S-半胱氨酸-DA/DA 比值。基于 5-S-半胱氨酸-DA/DA 比值，发现尾状核中的多巴胺氧化随年龄呈统计学显著增加，而黑质中的多巴胺氧化则无显著增加。总之，在人类多巴胺能脑区中证明了 5-S-半胱氨酸-DA、5-S-半胱氨酸-DOPAC 和 5-S-半胱氨酸-DOPA 的存在，与对照组相比，帕金森病组的 DA 氧化程度较高，并且随着年龄的增长，DA 氧化呈统计学显著增加。可能的情况是，DA 和其他儿茶酚的自动氧化参与了大脑的正常和病理衰老。本研究证实了一项较早但规模较小的研究，以及一项对非帕金森病例的研究、一项对帕金森病例和对照组的 NM 结合或整合标志物或儿茶酚的研究。
