Functional studies in lymphocytes from Amyotrophic Lateral Sclerosis patients: relevance to biomarkers determination

• Grant number: 18/09084-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2018
• Effective date (End): November 30, 2018
• Field of knowledge: Interdisciplinary Subjects
• Principal researcher: Tatiana Rosado Rosenstock
• Grantee: Beatriz Grisolia Araujo
• Home 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

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons. Mostly, ALS is a sporadic disease, and only between 10 to 15% of the cases is familial (due to genetic reasons; named ALSf). Nowadays it is known that ALS etiology is multifactorial, since it does not only present changes in genic expression and an increase in ubiquitinated proteins inclusion, but also modification in energetic cellular status - one of the main neuropathological features. Thus, of great importance for this project is the fact that it was already described changes in mitochondrial function in several animal models of ALS, as well as in patient samples, namely cytochrome c oxidase mutation, mitochondrial DNA (DNAmt) deletion and increase in mitochondrial fission. Interestingly, at the same time, there is few data in the literature about the factors related to the ALS progression, in human, and, mainly, which is the correlation among them and mitochondrial function changes along time. Therefore, the goal of this project is to perform I) a control-case study and II) a prospective-cohort study, with samples from ASL patients from the Neurology department at Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), focusing in unveil the role of mitochondrial function and energetic metabolism to the progression of ALS symptoms. Therefore, we believe that this study will disclose the mitochondrial dysfunction per se and/or changes in other factors indirectly linked to mitochondrial dysfunction as a biomarker to ALS prognosis and therapeutic evaluation.

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)

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. 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.