Novel Protective Effects of Estradiol Metabolites in Alzheimer’s Disease

Principal Investigator: Lefteris Zacharia

Affiliation: School of Sciences and Engineering, Life and Health Sciences, University of Nicosia.

 

Aims and Objectives

​Alzheimer’s Disease (AD) is a complex neurodegenerative disorder, characterized by progressive cognitive impairment and memory loss affecting the elderly. It is characterized by the formation of amyloid plaques, tangles, and neuronal death.


 

  • Interestingly, it has been shown that depletion of estrogens in women facilitates vulnerability to AD pathogenesis.  Delineating estradiol’s mechanism of action, may further lead to the identification of novel therapeutic targets and pave the way for new preventive measures for AD.  More importantly, as these E2 metabolites are not feminizing, they can be used therapeutically in men as well as women without feminizing adverse effects.

  • The particular study attempted to provide the necessary proof of principle needed to open new avenues in AD treatment.

Outcomes - Summary

​Available scientific evidence suggests that estradiol is protective, while other synthetic hormones that are given to menopausal women to supplement astradiol are not as effective. It was hypothesized that estradiol may be effective because of the way it gets metabolized to a number of other compounds (metabolites), some of which have beneficial effects in many systems such as the cardiovascular system. Accordingly, the aim of this project was to investigate whether these metabolites derived from the female hormone estradiol do indeed protect from Alzheimer disease (AD) progression and if they do, determine how they protect. The findings indicate that estradiol metabolites may offer significant protection by mechanisms distinct from those of estradiol.