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Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models

Grant number: 16/20796-2
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2017 - October 31, 2022
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Rodrigo Portes Ureshino
Grantee:Rodrigo Portes Ureshino
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Assoc. researchers:Catarina Segreti Porto ; Gustavo José da Silva Pereira ; Soraya Soubhi Smaili
Associated grant(s):20/04709-8 - Evaluation of potential therapeutically compounds for SARS-CoV-2: focus on estrogen-related compounds, autophagy modulators and ACE2, AP.R
Associated scholarship(s):21/01350-1 - Husbandry and handling of zebrafish model in a rack system, BP.TT
19/20131-9 - Study of intracellular signalling and metabolism mediated by estrogen in a neurodegeneration cell model, BP.MS
19/19176-8 - Husbandry and handling of zebrafish model in a rack system, BP.TT
+ associated scholarships 19/11546-0 - Study of the estrogen-modulated autophagy in a neurodegeneration model by tau protein superexpression in zebrafish, BP.MS
18/06260-8 - Study of cannabinoid compounds modulation in the autophagy mediated by TFEB in a cellular Tauophathy model, BP.DR
18/09925-0 - 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, BP.IC
18/16719-8 - The role of estrogen receptors in autophagy in cellular model of Tauopathy, BP.DD
17/23616-8 - Analysis of progestagen receptors-mediated autophagy against tau toxicity in cell model of tauopathy, BP.PD
18/02762-9 - Evaluation of estrogen-mediated neuroprotection in cellular model of the tauopathy, BP.MS - associated scholarships

Abstract

Many studies have shown the effects of estrogens in neuroprotection in neurodegenerative processes, such as in Alzheimer's Disease. Furthermore, modulation of autophagy is one of the promising strategies for the treatment of dementias associated with the formation of protein aggregates, which occur in Tauopathies, where the main component is the tau protein. However, the role of estrogens in regulating autophagy has to be elucidated in the central nervous system. Thus, this project aims to investigate the involvement of estrogen receptors ER-alpha, ER-beta and GPER in the modulation of autophagy pathways, focusing on cellular protection in cell and animal models of neurodegenerative disease. In the first part of the project it will be established and characterized a cellular model of neurons overexpressing human tau protein. The autophagy induction mediated by activation/inhibition will be evaluated, searching for compounds that are able to reduce the protein accumulation. In parallel, it will be studied the intracellular signaling and bioenergetics modulated by activation/inhibition of estrogen receptors, by using pharmacological approaches, as well as knockout of estrogen receptors. In the second part of the project it will be used a Zebrafish model to study the role of estrogen receptors in the induction of autophagy in vivo, and subsequently the possible neuroprotective role against the human tau protein. Thus, considering that the regulation of estrogen receptor plays an important role in cytoprotection, its interrelation with the autophagy process can open new possibilities of combination therapy for dementia, as occurs in Alzheimer's Disease. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RODRIGUES LEMES, ROBERTHA MARIANA; COSTA, ANGELICA JARDIM; BARTOLOMEO, CYNTHIA SILVA; BASSANI, TAYSA BERVIAN; NISHINO, MICHELLE SAYURI; DA SILVA PEREIRA, GUSTAVO JOSE; SMAILI, SORAYA SOUBHI; DE BARROS MACIEL, RUI MONTEIRO; BRACONI, CARLA TORRES; DA CRUZ, EDGAR FERREIRA; RAMIREZ, ANA LOPEZ; MARICATTO, JULIANA TERZI; RAMOS JANINI, LUIZ MARIO; PRADO, CARLA MAXIMO; STILHANO, ROBERTA SESSA; URESHINO, RODRIGO PORTES. 17 beta-estradiol reduces SARS-CoV-2 infection in vitro. PHYSIOLOGICAL REPORTS, v. 9, n. 2 JAN 2021. Web of Science Citations: 0.
STILHANO, ROBERTA SESSA; COSTA, ANGELICA JARDIM; NISHINO, MICHELLE SAYURI; SHAMS, SHAHIN; BARTOLOMEO, CYNTHIA SILVA; BREITHAUPT-FALOPPA, ANA CRISTINA; SILVA, EDUARDO ALEXANDRE; RAMIREZ, ANA LOPEZ; PRADO, CARLA MAXIMO; URESHINO, RODRIGO PORTES. SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors. FASEB JOURNAL, v. 34, n. 11, p. 14103-14119, NOV 2020. Web of Science Citations: 3.
NASCIMENTO, ANA CAROLINA; ERUSTES, ADOLFO G.; RECKZIEGEL, PATRICIA; BINCOLETTO, CLAUDIA; URESHINO, RODRIGO P.; PEREIRA, GUSTAVO J. S.; SMAILI, SORAYA S. alpha-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y. Neurochemical Research, SEP 2020. Web of Science Citations: 0.
URESHINO, RODRIGO PORTES; ERUSTES, ADOLFO GARCIA; BASSANI, TAYSA BERVIAN; WACHILEWSKI, PATRICIA; GUARACHE, GABRIEL CICOLIN; NASCIMENTO, ANA CAROLINA; COSTA, ANGELICA JARDIM; SMAILI, SORAYA SOUBHI; DA SILVA PEREIRA, GUSTAVO JOSE. The Interplay between Ca2+ Signaling Pathways and Neurodegeneration. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 23 DEC 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.