Neuroprotective potential evaluation of a synthetic peptide in neurodegenerative diseases: evaluation of genotoxicity and mutagenicity

• Grant number: 15/24808-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2016
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Antonio Cardozo dos Santos
• Grantee: Carolina Petri Bernardes
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM

Abstract

Neurodegenerative diseases are major causes of morbidity and mortality in Western countries. Common mechanisms of toxicity involving mitochondrial damage have been suggested, however, a definitive treatment has yet been found. Therefore, there has been a great interest in the development of neuroprotective compounds for the treatment of neurodegenerative diseases. Toxins animals represent a promising source of novel molecules with neuroprotective activity and potential to create new drugs. Such molecules are well known, can be used as important elements in the investigation of cellular and molecular mechanisms. Thus, this study aims at the synthesis of a peptide with neuroprotective effects and some analogues, using as a model a peptide recently isolated by our research group, from Bothrops atrox snake venom. The synthetic peptide suffer specific modifications such as charge modification of the molecule either at the C-terminal portion and the N-terminal portion, with the aim of improving the interaction with the target and thus increase the peptide efficiently as their neuroprotective activity. The synthetic peptide and their analogs are evaluated for: 1. the neuroprotective in vitro, in cell models for Parkinson and Alzheimer disease, 2- expression of proteins involved in apoptosis and cell differentiation, 3- signaling cellular pathways as TRK, MAPK / ERK and PI3K / AKT / mTOR. In addition, the peptides will be evaluated for potential to induce cell damage by cytotoxic potential determinations, genotoxic and mutagenic, since the objective is to develop biomolecules to obtain new drugs. The results of this project will thus increase knowledge related to the mechanisms of action of venom peptides in cellular models for Parkinson's and Alzheimer's disease. (AU)

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)

BERNARDES, CAROLINA P.; SANTOS, NEIFE A. G.; COSTA, TASSIA R.; SISTI, FLAVIA; AMARAL, LILIAN; MENALDO, DANILO L.; AMSTALDEN, MARTIN K.; RIBEIRO, DIEGO L.; ANTUNES, LUSANIA M. G.; SAMPAIO, SUELY VILELA; et al. A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics. NEUROTOXICITY RESEARCH, OCT 2019. (15/24808-2, 11/23236-4)

BERNARDES, CAROLINA P.; SANTOS, NEIFE A. G.; COSTA, TASSIA R.; SISTI, FLAVIA; AMARAL, LILIAN; MENALDO, DANILO L.; AMSTALDEN, MARTIN K.; RIBEIRO, DIEGO L.; ANTUNES, LUSANIA M. G.; SAMPAIO, SUELY VILELA; et al. A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics. NEUROTOXICITY RESEARCH, v. 37, n. 1, p. 11-pg., 2019-10-25. (11/23236-4, 15/24808-2)