2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson's Disease

Estrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Methoxestradiol (2-ME2), a 17 & beta;-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 17 & beta;-estradiol and its metabolites as biomarkers in the diagnosis of neurodegenerative diseases, no. P.441360.

Automated summary

2-ME2, a metabolite of 17-β-estradiol, has anticancer effects, but may promote neurodegenerative diseases like Parkinson's disease in the central nervous system. It generates nitro-oxidative stress, controls heat shock proteins, and leads to DNA strand breakage and apoptosis. Plasma levels of methoxyestrogens and hydrogen peroxide may serve as novel biomarkers for Parkinson's disease.