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Effect of NAADP in autophagic signaling regulated by mTOR (mammalian Target of Rapamycin) in astrocytes

Grant number: 13/01769-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): April 30, 2014
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Soraya Soubhi Smaili
Grantee:Gustavo José da Silva Pereira
Supervisor abroad: Gian Maria Fimia
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Research place: Università degli Studi di Roma Tor Vergata, Italy  
Associated to the scholarship:10/11165-2 - NAADP: A New Second Messenger Ca2+ Mobilizator and Autophagy Regulator, BP.DR


Autophagy is a catabolic process essential for the turnover of cytosolic proteins and organelles. It involves the formation of a double membrane structure known as the autophagosome around a targeted region of the cytosol. The Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+ mobilizing messenger that in many cells releases Ca2+ from the endo-lysosomal system, this effect is mediated by the two-pore channels (TPCs), especially TPC type 2. Whether NAADP acts as a messenger in astrocytes is unclear and the functions on autophagy have yet to be defined. In our present work, the effects of NAADP and the relationship of this event in autophagy regulation with the mTOR pathway remains to be studied. Several evidences provide that NAADP-evoked Ca2+ signals might regulate autophagy on the first (by mTOR pathway) and the last step (by p62 modulation). Therefore, the objective of this work is to investigate the autophagic intracellular pathways mediated by NAADP in murine astrocytes, and the possible interrelationship with mTOR via. For this purpose, we will evaluate autophagy modulation by confocal microscopy, flow cytometer and the expression of genes and proteins related to these pathways, which will be analyzed by molecular biology techniques. (AU)

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Scientific publications
(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)
PEREIRA, GUSTAVO J. S.; ANTONIOLI, MANUELA; HIRATA, HANAKO; URESHINO, RODRIGO P.; NASCIMENTO, ALINE R.; BINCOLETTO, CLAUDIA; VESCOVO, TIZIANA; PIACENTINI, MAURO; FIMIA, GIAN MARIA; SMAILI, SORAYA S.. Glutamate induces autophagy via the two-pore channels in neural cells. ONCOTARGET, v. 8, n. 8, p. 12730-12740, . (13/01769-6, 08/11515-3, 13/20073-2)

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