Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway

Autor(es)

Carolina Petri Bernardes ^[1] ; Ernesto Lopes Pinheiro Junior ^[2] ; Isabela Gobbo Ferreira ^[3] ; Isadora Sousa de Oliveira ^[4] ; Neife Aparecida Guinaim dos Santos ^[5] ; Suely Vilela Sampaio ^[6] ; Eliane Candiani Arantes ^[7] ; Antonio Cardozo dos Santos ^[8]

Afiliação do(s) autor(es)

^[1] University of São Paulo. Department of Clinical Analyses, Toxicology and Food Science. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[2] University of São Paulo. Department of Biomolecular Sciences. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[3] University of São Paulo. Department of Biomolecular Sciences. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[4] University of São Paulo. Department of Biomolecular Sciences. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[5] University of São Paulo. Department of Clinical Analyses, Toxicology and Food Science. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[6] University of São Paulo. Department of Clinical Analyses, Toxicology and Food Science. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[7] University of São Paulo. Department of Biomolecular Sciences. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

^[8] University of São Paulo. Department of Clinical Analyses, Toxicology and Food Science. School of Pharmaceutical Sciences of Ribeirão Preto - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 30, 2024-06-14.

Resumo

Abstract Background: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of Crotalus durissus collilineatus venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet. Methods: We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP+ (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models. Results: Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP+ on cell viability and differentiation. Conclusion: These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models. (AU)

• Processo FAPESP: 19/10173-6 - Produção, modificação e caracterização de toxinas animais com potencial aplicação biotecnológica
• Beneficiário: Eliane Candiani Arantes Braga
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/13176-3 - Descoberta de anticorpos monoclonais humanos (scFv) com reatividade cruzada e pH-dependentes para as metaloproteases de Bothrops spp
• Beneficiário: Isadora Sousa de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado