The effect of DNA methylation inhibitors on 1-methyl-4-phenylpyridinium iodide (MPP +) induced neurotoxicity in cultured neuronal cells model.

• Grant number: 15/05530-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2015
• End date: March 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Sâmia Regiane Lourenço Joca
• Grantee: Rebeca Araujo Cantelmo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The DNA may change due to mutations that occur directly in the genome or by external influences (epigenetic mechanisms). Epigenetic changes are responsible for gene interpretation, embryonic development, cell differentiation, maintenance of cell identity and regulatory responses to external stimuli. There are numerous epigenetic mechanisms may modify the state of condensation of chromatin and interfere with gene expression: DNA methylation, post-translational modification of histones and mechanisms related to RNA. The DNA methylation, the most common mechanism among mammals, occurs when a methyl group is added predominantly in the 5'-position of the pyrimidine ring of cytokines that carry out guanines in regions where there are dinucleotide CpG islands. This reaction is catalyzed by a group of enzymes called DNA methyl transferases (DNMT), which transfer this methyl group originated from S-adenosylmethionine group (SAM). This process varies over time and increases with age. There is evidence that DNA methylation is an important biological mechanism for the establishment of changes in gene expression that can contribute to the development of neurodegenerative diseases such as Parkinson's disease (PD). However, no data on the effect of drugs that modify DNA methylation on the neurodegenerative processes associated with PD. Therefore, this work has as main objective to evaluate the effect of administration of DNMTs inhibitors (5-aza-D and RG108) on cell viability and neuritogenesis in neuronal cell line (PC12 cells) treated with the neurotoxin dopaminergic MPP + (1-Methyl-4-phenylpyridinium iodide), a neurodegeneration model that simulates in vitro cellular mechanisms associated with PD.

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)

CANTELMO, REBECA ARAUJO; DOS SANTOS, NEIFE APARECIDA G.; DOS SANTOS, ANTONIO CARDOZO; JOCA, SAMIA REGIANE LOURENCO. Dual effects of S-adenosyl-methyonine on PC12 cells exposed to the dopaminergic neurotoxin MPP+. Journal of Pharmacy and Pharmacology, v. 72, n. 10, JUN 2020. (15/05530-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CANTELMO, Rebeca Araujo. The effect of DNA methylation inhibitors on 1-methyl-4-phenylpyridinium iodide (MPP +) induced neurotoxicity in cultured neuronal cells model. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.