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dc.contributor.authorBernardes, Carolina P.
dc.contributor.authorSantos, Neife A. G.
dc.contributor.authorSisti, Flavia M.
dc.contributor.authorFerreira, Rafaela Scalco
dc.contributor.authorSantos-Filho, Norival A. [UNESP]
dc.contributor.authorCintra, Adelia C. O. [UNESP]
dc.contributor.authorCilli, Eduardo M. [UNESP]
dc.contributor.authorSampaio, Suely
dc.contributor.authorSantos, Antonio C.
dc.date.accessioned2018-11-26T22:38:12Z
dc.date.available2018-11-26T22:38:12Z
dc.date.issued2018-06-01
dc.identifierhttp://dx.doi.org/10.1016/j.peptides.2018.04.012
dc.identifier.citationPeptides. New York: Elsevier Science Inc, v. 104, p. 24-34, 2018.
dc.identifier.issn0196-9781
dc.identifier.urihttp://hdl.handle.net/11449/164807
dc.description.abstractVenom 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.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent24-34
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofPeptides
dc.sourceWeb of Science
dc.subjectSnake-venom peptides
dc.subjectNeuroprotection
dc.subjectNeurotrophin receptors trkA (tropomyosin receptor kinase A)
dc.subjectMPP+ (1-methyl-4-phenylpyridinium)
dc.subjectPC12 cells
dc.titleA synthetic snake-venom-based tripeptide (Glu-Val-Trp) protects PC12 cells from MPP+ toxicity by activating the NGF-signaling pathwayen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.description.affiliationUniv Sao Paulo, FCFRP, Dept Anal Clin Toxicol & Bromatol, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, UNESP, Inst Quim Araraquara, Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, UNESP, Inst Quim Araraquara, Araraquara, SP, Brazil
dc.identifier.doi10.1016/j.peptides.2018.04.012
dc.identifier.wosWOS:000432591600004
dc.rights.accessRightsAcesso aberto
dc.description.sponsorshipIdFAPESP: 2015/4808-2
dc.description.sponsorshipIdFAPESP: 2011/23236-4
dc.description.sponsorshipIdFAPESP: 2013/07600-3
dc.identifier.fileWOS000432591600004.pdf
dc.relation.ispartofsjr1,001
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