Advanced search
Start date
Betweenand

The role of lysine(K)-deacetylases on mitochondrial disorders's neuroprotection: perspectives of epigenetic therapy for amyotrophic lateral sclerosis and schizophrenia

Grant number: 15/02041-1
Support type:Research Grants - Young Investigators Grants
Duration: April 01, 2016 - June 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Tatiana Rosado Rosenstock
Grantee:Tatiana Rosado Rosenstock
Home Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil
Assoc. researchers:Clélia Rejane Antõnio ; Cristoforo Scavone ; Isaias Glezer
Associated grant(s):18/08399-3 - Age-related mitochondrial metabolism and its relationship with neurogenesis in an animal model of schizophrenia, AP.R SPRINT
Associated scholarship(s):19/17725-4 - The role of mitochondrial degradation to cellular homeostasis: a study in patients stem cells (iPSC) with familial Amyotrophic Lateral Sclerosis, BP.IC
18/09084-6 - Functional studies in lymphocytes from Amyotrophic Lateral Sclerosis patients: relevance to biomarkers determination, BP.IC
17/02295-9 - Mitochondrial dynamics and degradation in schizophrenia models, BP.IC
16/12039-7 - Lysine(K)-deacetylases modulation and its role in mitochondrial metabolism, dynamics and degradation: possible neuroprotection for Amyotrophic Lateral Sclerosis, BP.MS

Abstract

Because lysine(K)-deacetylases (KDACs) regulate proteins involved in mechanisms such as gene transcription, cellular clearance and metabolism, in which mitochondria plays an essential role, the aim of this project is to characterize the role of KDACs on mitochondrial function and degradation (mitophagy) in different models of Amyotrophic Lateral Sclerosis (ALS) and Schizophrenia (SHZ); it is known that mitochondria is related to the etiology and/or progression of these disorders. In addition, it is described that KDACs being the main responsible for epigenetic modification, it becomes the major key between molecular events and behavioral alterations; therefore, it will be also evaluated the role of KDACs as neuroprotective agents. To reach the goals proposed herein, neurons and astrocytes from hSOD1 G93A and SHR rats and immortalized cells in the presence or absence of mutant SOD1 and DISC-1 will be treated with different KDACs modulators and/or will be transfected with plasmids, si- or shRNAs against specifics KDACs. Thus, it is expected that this project discloses the neuroprotection role of KDAC in the two major brain cellular types and, as a consequence, new therapeutic tools could be developed. Hence, epigenetic modifications against mitochondrial dysfunction may possibly be the target of future projects (GraphAbstract - ATTACHMENT I). (AU)

Articles published in Agência FAPESP Newsletter about the research grant
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
Articles published in other media outlets (18 total):
More itemsLess items
La falta de oxígeno en la gestación puede causar esquizofrenia 
Hipóxia durante a gravidez pode causar esquizofrenia 
Falta de oxigênio pode causar esquizofrenia 
Estudo constata hipóxia durante a gravidez causa esquizofrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
This study shows how a lack of oxygen during pregnancy can cause schizophrenia 
Falta de oxigênio na gestação pode ser uma das causas da esquizofrenia 
Grupo investiga como a falta de oxigênio na gestação pode causar esquizofrenia 
Grupo investiga como falta de oxigênio na gestação pode causar esquizofrenia 
Grupo investiga como falta de oxigênio na gestação pode causar esquizofrenia 
Falta de oxigênio na gestação pode ser uma das causas da esquizofrenia 
Estudo analisa como falta de oxigênio na gestação pode causar esquizofrenia 
Falta de oxigênio na gestação pode ser uma das causas da esquizofrenia 

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)
SOUZA E SILVA, LUIZ FELIPE; BRITO, MARIANA DUTRA; CAMARGO YUZAWA, JESSICA MAYUMI; ROSENSTOCK, TATIANA ROSADO. Mitochondrial Dysfunction and Changes in High-Energy Compounds in Different Cellular Models Associated to Hypoxia: Implication to Schizophrenia. SCIENTIFIC REPORTS, v. 9, DEC 2 2019. Web of Science Citations: 0.
BRITO, MARIANA DUTRA; GOMES DA SILVA, GUSTAVO FERRO; TILIERI, ERICK MUTTI; ARAUJO, BEATRIZ GRISOLIA; CALIO, MICHELE LONGONI; ROSENSTOCK, TATIANA ROSADO. Metabolic Alteration and Amyotrophic Lateral Sclerosis Outcome: A Systematic Review. FRONTIERS IN NEUROLOGY, v. 10, NOV 20 2019. Web of Science Citations: 0.

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