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Establishment of a Hek-293 cell model to study the estrogenic signaling mediated by xenoestrogens in the autophagy activation: a link with Tauopathies cell models

Grant number: 18/09925-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2018
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Rodrigo Portes Ureshino
Grantee:Ana Beatriz Alves da Conceição
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Associated research grant:16/20796-2 - Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models, AP.JP

Abstract

Several studies have evaluated the neuroprotective role of estrogens in neurodegenerative diseases, such as Alzheimer's disease. However, chronic exposure to environmental xenoestrogens are related to carcinogenicity and neurotoxicity, which can be a result of endocrine system demise. It is already known that the modulation of autophagy is a promising strategy for the treatment of dementias associated with protein aggregates, which occurs in tauopathies, and the blockage of this catabolic process can lead to neurodegeneration. On the other hand, the role of estrogens in the regulation of autophagy is poorly understood, especially in the central nervous system, as well as the exposure to subtoxic doses of xenoestrogens in neurodegeneration. Therefore, this project aims to investigate the involvement of ERalpha, ERbeta and GPER estrogen receptors in the modulation of xenoestrogen-induced autophagy pathways, such as bisphenol A exposure, which may be also applied to neurodegenerative disease model. The first step will be the establishment and characterization of a HEK-293 cell line overexpressing individually the estrogen receptors. Thereafter, autophagy pathway modulated by xenoestrogens will be studied, evaluating the estrogen receptors activation or inhibition. As a future perspective of this project, we will evaluate the role of xenoestrogens in a cell model of tauopathies. Thus, considering that xenoestrogens can regulates estrogen receptors, its interrelationship with the autophagy process could contribute to the understanding of diseases associated with protein accumulation, such as in Alzheimer's disease.