雌激素在许多生理过程中发挥作用，包括控制脑细胞的生长和分化。2-甲氧基雌二醇（2-ME2）是一种17β-雌二醇（E2）代谢物，据观察其具有抗癌作用，无论在体内或体外都有表现。2-ME2影响所有活跃分裂的细胞，包括神经元。本研究旨在确定2-ME2在特定组织培养模型和临床环境中是否是一种具有潜在抗癌保护作用或神经退行性作用的药物。在本研究中，通过神经母细胞瘤SH-SY5Y细胞系的帕金森病（PD）体外模型，确定了2-ME2的活性。所得结果表明，2-ME2产生亚硝基氧化应激反应，并控制热休克蛋白（HSP），导致DNA链断裂和凋亡。从一方面来看，它可能影响强烈分裂的细胞，预防癌症的发展；然而，这种活性在中枢神经系统内可能促进帕金森病等神经退行性疾病的发生。因此，还研究了2-ME2的神经毒性活性在PD体外模型中的转化价值。采用LC-MS/MS技术评估了PD患者血液中的雌激素及其衍生物，即羟基和甲氧基雌激素，使用停流法评估了过氧化氢（H2O2）水平。与对照组相比，患者血液中的甲氧基雌激素和H2O2水平增加，而羟基雌激素同时减少。根据上述结果，我们认为测定甲氧基雌激素和H2O2的血浆水平可能是一种新的PD生物标志物。所述研究是挂号专利申请 "利用过氧化氢和17β-雌二醇及其代谢物在神经退行性疾病诊断中的应用" ，编号P.441360。©2023作者。

Estrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Methoxestradiol (2-ME2), a 17β-estradiol (E2) metabolite, is known for its anticancer effects as observed both in vivo and in vitro. 2-ME2 affects all actively dividing cells, including neurons. The study aimed to determine whether 2-ME2 is a potentially cancer-protective or rather neurodegenerative agent in a specific tissue culture model as well as a clinical setup. In this study, 2-ME2 activity was determined in a Parkinson's disease (PD) in vitro model based on the neuroblastoma SH-SY5Y cell line. The obtained results suggest that 2-ME2 generates nitro-oxidative stress and controls heat shock proteins (HSP), resulting in DNA strand breakage and apoptosis. On the one hand, it may affect intensely dividing cells preventing cancer development; however, on the other hand, this kind of activity within the central nervous system may promote neurodegenerative diseases like PD. Thus, the translational value of 2-ME2's neurotoxic activity in a PD in vitro model was also investigated. LC-MS/MS technique was used to evaluate estrogens and their derivatives, namely, hydroxy and methoxyestrogens, in PD patients' blood, whereas the stopped-flow method was used to assess hydrogen peroxide (H2O2) levels. Methoxyestrogens and H2O2 levels were increased in patients' blood as compared to control subjects, but hydoxyestrogens were simultaneously decreased. From the above, we suggest that the determination of plasma levels of methoxyestrogens and H2O2 may be a novel PD biomarker. The presented research is the subject of the pending patent application "The use of hydrogen peroxide and 17β-estradiol and its metabolites as biomarkers in the diagnosis of neurodegenerative diseases," no. P.441360.© 2023. The Author(s).