Lysine(K)-deacetylases modulation and its role in mitochondrial metabolism, dynamics and degradation: possible neuroprotection for amyotrophic lateral sclerosis

• Grant number: 16/12039-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2016
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Tatiana Rosado Rosenstock
• Grantee: Mariana Dutra Brito
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil
• Associated research grant: 15/02041-1 - The role of lysine(K)-deacetylases on mitochondrial disorders's neuroprotection: perspectives of epigenetic therapy for amyotrophic lateral sclerosis and schizophrenia, AP.JP

Abstract

One of the major concerns related to neurodegenerative diseases is the development of neuroprotective strategies. Concerning to that, epigenetic modification is one of the most promising; in fact, lysine (K) acetylation is a highlighted topic. 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); it is known that mitochondria is related to the etiology and/or progression of this disorder. ALS is characterized by progressive motor neuron degeneration and, despite of the most cases of the disease are sporadic (90%), a small percentage is due to genetic factors (familial cases; FALS). From FALS, 15-20% of the cases are related to a mutation in the superoxide dismutase Cu/Zn (SOD1) gene, an antioxidant enzyme. However, ALS is still considered a multifactorial disorder since it presents not only changes in genic expression and increase in oxidative stress, but also excitotoxicity and mitochondrial dysfunction. To reach the goal proposed herein, neurons and/or astrocytes from hSOD1 G93A rats and immortalized cells, SH-SY5Y, in the presence or absence of mutated SOD1 will be used. Altogether, new therapeutic strategies could be developed targeting neuroprotection through augmentation of mitochondrial function and/or mitophagy. (AU)

Scientific publications

(5)

(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)

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, AUG 2020. (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, NOV 20 2019. (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, DEC 2 2019. (15/02041-1, 16/12039-7, 15/25595-2)

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., 2020-08-25. (15/02041-1, 16/12039-7, 15/25595-2, 18/09084-6)

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, JUL 2021. (16/12039-7, 15/02041-1)