Department of Neurology, University Clinic Bonn, Bonn, Germany; Department of Ophthalmology, University Clinic Bonn, Bonn, Germany.
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam, Rehbruecke (DIfE), 14558, Nuthetal, Germany.
Redox Biol. 2020 Jul;34:101546. doi: 10.1016/j.redox.2020.101546. Epub 2020 May 18.
Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to neuronal demise appears to represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) trigger the accumulation of such modified proteins, which eventually contributes to pathological aspect of NDDs. Increased levels of AGEs are found in amyloid plaques in AD brains and in both advanced and early PD (incidental Lewy body disease). The molecular mechanisms by which AGE dependent modifications may modulate the susceptibility towards NDDs, however, remain enigmatic and it is unclear, whether AGEs may serve as biomarker of NDD. In the present study, we examined AGEs (CML: Carboxymethyllysine and CEL: Carboxyethyllysine), markers of oxidative stress and micronutrients in the plasma of PD and AD patients and controls. As compared to healthy controls, AD females displayed lower levels of CEL while higher levels of CML were found in AD and PD patients. A somewhat similar pattern was observed for protein carbonyls (PC), revealing lower values exclusively in AD females, whereas AD males displayed significantly higher values compared to healthy controls and PD. Sex-specific differences were also observed for other relevant markers such as malondialdehyde, 3-nitrotyrosine, γ -tocopherols, retinol, plasma proteins and α-carotene, while α-tocopherols, β-carotene, lutein/zeaxanthin, β-cryptoxanthin and lycopene showed no relevant association. Taken together, our study suggests yet unappreciated differences of the distribution of AGEs among the sexes in NDD. We therefore suggest to make a clear distinction between sexes when analyzing oxidative (AGEs)-related stress and carbonyl-related stress and vitamins.
神经退行性疾病（NDD），如阿尔茨海默病（AD）和帕金森病（PD），是不同的临床实体，然而，关键神经元蛋白的聚集，可能导致神经元死亡，这似乎代表了一种共同的机制。已经很明显，晚期糖基化终产物（AGEs）触发了这些修饰蛋白的积累，这最终导致了 NDD 的病理方面。在 AD 大脑中的淀粉样斑块和 PD（偶然的路易体病）的早期和晚期都发现了高水平的 AGEs。然而，AGE 依赖性修饰可能调节对 NDD 的易感性的分子机制仍然是神秘的，并且不清楚 AGEs 是否可以作为 NDD 的生物标志物。在本研究中，我们检查了 PD 和 AD 患者和对照组的血浆中的 AGEs（CML：羧甲基赖氨酸和 CEL：羧乙基赖氨酸）、氧化应激标志物和微量营养素。与健康对照组相比，AD 女性的 CEL 水平较低，而 AD 和 PD 患者的 CML 水平较高。蛋白质羰基（PC）也观察到了类似的模式，AD 女性的数值明显较低，而 AD 男性与健康对照组和 PD 相比，数值明显较高。其他相关标志物，如丙二醛、3-硝基酪氨酸、γ-生育酚、视黄醇、血浆蛋白和α-胡萝卜素，也观察到了性别特异性差异，而α-生育酚、β-胡萝卜素、叶黄素/玉米黄质、β-隐黄质和番茄红素则没有表现出相关的关联。总的来说，我们的研究表明，在 NDD 中，AGEs 在性别之间的分布存在尚未被认识到的差异。因此，我们建议在分析与氧化（AGEs）相关的应激和羰基相关的应激和维生素时，明确区分性别。
