Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A synthetic snake-venom-based tripeptide (Glu-Val-Trp) protects PC12 cells from MPP+ toxicity by activating the NGF-signaling pathway

Full text
Bernardes, Carolina P. [1] ; Santos, Neife A. G. [1] ; Sisti, Flavia M. [1] ; Ferreira, Rafaela Scalco [1] ; Santos-Filho, Norival A. [2] ; Cintra, Adelia C. O. [2] ; Cilli, Eduardo M. [2] ; Sampaio, V, Suely ; Santos, Antonio C. [3]
Total Authors: 9
[1] Univ Sao Paulo, FCFRP, Dept Anal Clin Toxicol & Bromatol, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Estadual Paulista, UNESP, Inst Quim Araraquara, Araraquara, SP - Brazil
[3] Sampaio, Suely, V, Univ Sao Paulo, FCFRP, Dept Anal Clin Toxicol & Bromatol, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Peptides; v. 104, p. 24-34, JUN 2018.
Web of Science Citations: 1

Venom small peptides that target neurotrophin receptors might be beneficial in neurodegeneration, including Parkinsons disease (PD). Their small size, ease of synthesis, structural stability and target selectivity make them important tools to overcome the limitations of endogenous neurotrophins as therapeutic agents. Additionally, they might be optimized to improve resistance to enzymatic degradation, bioavailability, potency and, mainly, lipophilicity, important to cross the blood brain barrier (BBB). Here, we evaluated the neuroprotective effects and mechanisms of the synthetic snake-venom-based peptide p-BTX-I (Glu-Val-Trp) in PC12 cells treated with MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that induces Parkinsonism in vivo. The peptide p-BTX-I induced neuritogenesis, which was reduced by (i) k252a, antagonist of the NGF-selective receptor, trkA (tropomyosin receptor kinase A); (ii) LY294002, inhibitor of the PI3 K/AKT pathway and (iii) U0126, inhibitor of the MAPK-ERK pathway. Besides that, p-BTX-I also increased the expression of GAP-43 and synapsin, which are molecular markers of axonal growth and synaptic communication. In addition, the peptide increased the viability and differentiation of cells exposed to MPP+, known to inhibit neuritogenesis. Altogether, our findings suggest that the synthetic peptide p-BTX-I protects PC12 cells from MPP+ toxicity by a mechanism that mimics the neurotrophic action of NGF. Therefore, the molecular structure of p-BTX-I might be relevant in the development of drugs aimed at restoring the axonal connectivity in neurodegenerative processes. (AU)

FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
Grantee:Suely Vilela
Support type: Research Projects - Thematic Grants