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

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)

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VEICULO: TITULO (DATA)

Scientific publications (14)
(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)
VARGA, THIAGO GARCIA; DE TOLEDO SIMOES, JUAN GUILHERME; SIENA, AMANDA; HENRIQUE, ELISANDRA; DA SILVA, REGINA CLAUDIA BARBOSA; DOS SANTOS BIONI, VINICIUS; RAMOS, ALINE CAMARGO; ROSENSTOCK, TATIANA ROSADO. Haloperidol rescues the schizophrenia-like phenotype in adulthood after rotenone administration in neonatal rats. Psychopharmacology, v. 238, n. 9, p. 2569-2585, . (19/17725-4, 15/02041-1, 15/26820-0)
CALIO, MICHELE LONGONI; HENRIQUES, ELISANDRA; SIENA, AMANDA; BERTONCINI, CLELIA REJANE ANTONIO; GIL-MOHAPEL, JOANA; ROSENSTOCK, TATIANA ROSADO. Mitochondrial Dysfunction, Neurogenesis, and Epigenetics: Putative Implications for Amyotrophic Lateral Sclerosis Neurodegeneration and Treatment. FRONTIERS IN NEUROSCIENCE, v. 14, . (15/02041-1)
VARGA, THIAGO GARCIA; DE TOLEDO SIMOES, JUAN GUILHERME; SIENA, AMANDA; HENRIQUE, ELISANDRA; DA SILVA, REGINA CLAUDIA BARBOSA; DOS SANTOS BIONI, VINICIUS; RAMOS, ALINE CAMARGO; ROSENSTOCK, TATIANA ROSADO. Haloperidol rescues the schizophrenia-like phenotype in adulthood after rotenone administration in neonatal rats. Psychopharmacology, . (15/02041-1, 15/26820-0, 19/17725-4)
ARAUJO, BEATRIZ GRISOLIA; SOUZA E SILVA, LUIZ FELIPE; TORRESI, JORGE LUIZ DE BARROS; SIENA, AMANDA; VALERIO, BERENICE CATALDO OLIVEIRA; BRITO, MARIANA DUTRA; ROSENSTOCK, TATIANA ROSADO. Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research. Molecular Neurobiology, . (15/02041-1, 18/09084-6, 15/25595-2, 16/12039-7)
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, . (15/02041-1, 16/12039-7, 18/09084-6)
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, . (15/02041-1, 16/12039-7, 15/25595-2)
SUN, CONGXIN; SERANOVA, ELENA; COHEN, MALKIEL A.; CHIPARA, MIRUNA; ROBERTS, JENNIE; ASTUTI, DEWI; PALHEGYI, ADINA M.; ACHARJEE, ANIMESH; SEDLACKOVA, LUCIA; KATAURA, TETSUSHI; et al. NAD depletion mediates cytotoxicity in human neurons with autophagy deficiency. CELL REPORTS, v. 42, n. 5, p. 27-pg., . (15/02041-1)
ARAUJO, BEATRIZ GRISOLIA; SOUZA E SILVA, LUIZ FELIPE; TORRESI, JORGE LUIZ DE BARROS; SIENA, AMANDA; VALERIO, BERENICE CATALDO OLIVEIRA; BRITO, MARIANA DUTRA; ROSENSTOCK, TATIANA ROSADO. Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research. Molecular Neurobiology, v. 57, n. 12, p. 19-pg., . (15/02041-1, 16/12039-7, 15/25595-2, 18/09084-6)
SIENA, AMANDA; YUZAWA, JESSICA MAYUMI; RAMOS, ALINE CAMARGO; HENRIQUE, ELISANDRA; DE SOUZA E SILVA, LUIZ FELIPE; BRITTO, MARIANA; ROSENSTOCK, TATIANA ROSADO. Neonatal Rotenone administration induces mitochondria metabolism and biogenesis deregulation leading to synaptic dynamics and behavioral alterations mimicking neurodevelopmental disorder. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, v. 49, p. 2-pg., . (15/02041-1)
SOUZA SILVA, LUIZ FELIPE; ROSENSTOCK, TATIANA ROSADO; CAMARGO YUZAWA, JESSICA MAYUMI. Hypoxia-induced mitochondrial metabolism deregulation associated to schizophrenia. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, v. 49, p. 2-pg., . (15/02041-1)
SIENA, AMANDA; YUZAWA, JESSICA MAYUMI CAMARGO; RAMOS, ALINE CAMARGO; HENRIQUE, ELISANDRA; BRITO, MARIANA DUTRA; CALVAZARA, MARIANA BENDLIN; ROSENSTOCK, TATIANA ROSADO. Neonatal Rotenone Administration Induces Psychiatric Disorder-Like Behavior and Changes in Mitochondrial Biogenesis and Synaptic Proteins in Adulthood. Molecular Neurobiology, v. 58, n. 7, p. 3015-3030, . (16/12039-7, 15/02041-1)
SILVA, LUIZ FELIPE SOUZA E; SIENA, AMANDA; YUZAWA, JESSICA MAYUMI; DE BARROS TORRESI, JORGE LUIZ; ZIROLDO, ALAN; ROSENSTOCK, TATIANA ROSADO. Sirtuins Modulators Counteract Mitochondrial Dysfunction in Cellular Models of Hypoxia: Relevance to Schizophrenia. Neuroscience, v. 524, p. 16-pg., . (15/02041-1, 15/25595-2, 18/13814-0, 19/17725-4)
GRISOLIA, BEATRIZ; BRITO, MARIANA; ROSENSTOCK, TATIANA. Mitochondrial function, biogenesis and dynamics deregulation in ALS patients PBMCs: a potential biomarker to enable a reliable prognosis. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, v. 49, p. 1-pg., . (15/02041-1)
ZATYKA, MALGORZATA; ROSENSTOCK, TATIANA R.; SUN, CONGXIN; PALHEGYI, ADINA M.; HUGHES, GEORGINA W.; LARA-REYNA, SAMUEL; ASTUTI, DEWI; DI MAIO, ALESSANDRO; SCIAUVAUD, AXEL; KORSGEN, MIRIAM E.; et al. Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome. STEM CELL REPORTS, v. 18, n. 5, p. 17-pg., . (15/02041-1)

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