Study of autophagy and neuroprotection in aging and in a Parkinson's Disease animal model

• Grant number: 12/08273-3
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2012
• Effective date (End): October 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Soraya Soubhi Smaili
• Grantee: Rodrigo Portes Ureshino
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 15/03507-4 - Evaluation of clinically-approved drugs to target tau toxicity in zebrafish model, BE.EP.PD

Abstract

Aging is a multifactorial process associated with functional deficits, and the brain is prone to chronic degenerative diseases, such as Parkinson's disease. Many studies have pointed autophagy as a strategy for neuroprotection in aging and in neurodegenerative diseases. In our laboratory we have been studying subcellular alterations related to cell death in the striatum during aging. We have lately studied autophagy in animal models of neurodegenerative diseases, such as Alzheimer's disease, and the possible role on neuroprotection against neurodegeneration (proc. FAPESP 2010/08437-0 e 2010/04280-0). In this work we investigated the process of autophagy and its relationship with the mechanisms of apoptosis or cell death. Furthermore, we evaluated the autophagy induction by using lithium as a pharmacological tool to neuroprotection in for Parkinson's disease model of young and aged animals. At first we will validate the treatments with behavioral tests in vivo and functional tissue evaluation in the striatum of these animals. The autophagy will be investigated by the expression of of the molecular markers. In addition, we will analyze the process by electron microscopy. In the second part of this project we will investigate the intracellular signaling pathways related to calcium organeles and autophagy. We will study by real time real space experiments in ex vivo slices. Furthermore, we will investigate the relationship between p53 and Parkin, since it has been demonstrated its participation in mitochondrial autophagy, known as mitophagy. Therefore, we will correlate the possible changes in the process of mitophagy with molecular alterations that are critical to the balance of cell life and cell death in the nigrostriatal pathway in aging as well as in neurodegeneration caused by Parkinson's disease. (AU)

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)

ANTUNES, FERNANDA; PEREIRA, GUSTAVO J. S.; SAITO, RENATA F.; BURI, V, MARCUS; GAGLIARDI, MARA; BINCOLETTO, CLAUDIA; CHAMMAS, ROGER; FIMIA, GIAN MARIA; PIACENTINI, MAURO; CORAZZARI, MARCO; et al. Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress. CELLS, v. 9, n. 3, MAR 2020. (13/20073-2, 17/10863-7, 12/08273-3)

URESHINO, RODRIGO PORTES; HSU, YI-TE; DO CARMO, LUCIA GARCEZ; YOKOMIZO, CESAR HENRIQUE; NANTES, ISELI LOURENCO; SMAILI, SORAYA SOUBHI. Inhibition of cytoplasmic p53 differentially modulates Ca2+ signaling and cellular viability in young and aged striata. Experimental Gerontology, v. 58, p. 120-127, OCT 2014. (13/20073-2, 12/08273-3)

COSTA, ANGELICA JARDIM; ERUSTES, ADOLFO GARCIA; SINIGAGLIA, RITA; NEVES GIRARDI, CARLOS EDUARDO; DA SILVA PEREIRA, GUSTAVO JOSE; URESHINO, RODRIGO PORTES; SMAILI, SORAYA SOUBHI. Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats. PHARMACEUTICS, v. 13, n. 2, FEB 2021. (17/10863-7, 12/08273-3, 16/20796-2, 13/20073-2, 13/20976-2)

URESHINO, RODRIGO PORTES; COSTA, ANGELICA JARDIM; ERUSTES, ADOLFO GARCIA; DA SILVA PEREIRA, GUSTAVO JOSE; SINIGAGLIA-COIMBRA, RITA; SMAILI, SORAYA SOUBHI. Effects of Aging in the Striatum and Substantia Nigra of a Parkinson's Disease Animal Model. TOXICOLOGIC PATHOLOGY, v. 46, n. 3, p. 348-358, APR 2018. (13/20073-2, 12/08273-3)