Carolina Petri Bernardes, Ernesto Lopes Pinheiro, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Neife Aparecida Guinaim Dos Santos, Suely Vilela Sampaio, Eliane Candiani Arantes, Antonio Cardozo Dos Santos
{"title":"含有crotapotin的C. d. collilineatus毒液馏分通过激活NGF信号通路保护PC12细胞免受MPP +的毒性。","authors":"Carolina Petri Bernardes, Ernesto Lopes Pinheiro, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Neife Aparecida Guinaim Dos Santos, Suely Vilela Sampaio, Eliane Candiani Arantes, Antonio Cardozo Dos Santos","doi":"10.1590/1678-9199-JVATITD-2023-0056","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 <i>Crotalus durissus collilineatus</i> 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.</p><p><strong>Methods: </strong>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<sup>+</sup> (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models.</p><p><strong>Results: </strong>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<sup>+</sup> on cell viability and differentiation.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194915/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fraction of <i>C. d. collilineatus</i> venom containing crotapotin protects PC12 cells against MPP <sup>+</sup> toxicity by activating the NGF-signaling pathway.\",\"authors\":\"Carolina Petri Bernardes, Ernesto Lopes Pinheiro, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Neife Aparecida Guinaim Dos Santos, Suely Vilela Sampaio, Eliane Candiani Arantes, Antonio Cardozo Dos Santos\",\"doi\":\"10.1590/1678-9199-JVATITD-2023-0056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 <i>Crotalus durissus collilineatus</i> 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.</p><p><strong>Methods: </strong>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<sup>+</sup> (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models.</p><p><strong>Results: </strong>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<sup>+</sup> on cell viability and differentiation.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":17565,\"journal\":{\"name\":\"Journal of Venomous Animals and Toxins Including Tropical Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194915/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Venomous Animals and Toxins Including Tropical Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/1678-9199-JVATITD-2023-0056\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Venomous Animals and Toxins Including Tropical Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1678-9199-JVATITD-2023-0056","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway.
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.
期刊介绍:
Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD) is a non-commercial academic open access publication dedicated to research on all aspects of toxinology, venomous animals and tropical diseases. Its interdisciplinary content includes original scientific articles covering research on toxins derived from animals, plants and microorganisms. Topics of interest include, but are not limited to:systematics and morphology of venomous animals;physiology, biochemistry, pharmacology and immunology of toxins;epidemiology, clinical aspects and treatment of envenoming by different animals, plants and microorganisms;development and evaluation of antivenoms and toxin-derivative products;epidemiology, clinical aspects and treatment of tropical diseases (caused by virus, bacteria, algae, fungi and parasites) including the neglected tropical diseases (NTDs) defined by the World Health Organization.