Systemic, Intrathecal, and Intracerebroventricular Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512–2 Toxin in Persistent Pain Models

Cavalli, Juliana; Assis, Pollyana Mendonça de; Gonçalves, Elaine Cristina Dalazen; Bobermin, Larissa Daniele; Quincozes‐Santos, André; Raposo, Nádia Rezende Barbosa; Gomez, Marcus V.; Dutra, Rafael C.

doi:10.1007/s12035-022-02864-w

Cited by 2 publications

(3 citation statements)

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“…These peptides have been evaluated in pre-clinical models and demonstrated interesting therapeutic efficacy in reverting or preventing conditions for which treatments are limited or unavailable. For example, ω-Pn2a and ω-Pn4a showed efficacy in treating painful neuropathies such as fibromyalgia and chronic post-ischemia pain, respectively ( Pedron et al, 2021 ; Cavalli et al, 2022 ), ω-Pn4a also improved motor movement and neuroprotection in Huntington’s disease ( Joviano-Santos et al, 2022 ). The engineered peptide PnPP-19 derived from the venom peptide δ-Pn2a was efficacious in treating glaucoma ( da Silva et al, 2020 ) and erectile dysfunction ( Nunes da Silva et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…This has been demonstrated for numerous spider venoms ( Smith et al, 2015 ; Cardoso and Lewis, 2018 , 2019 ), including the venom of the infamous South American ctenid spider Phoneutria nigriventer , often referred as Brazilian wandering spider, banana spider or “armed” spider ( Peigneur et al, 2018 ). Besides its clinical relevance due to frequent envenomation cases in Brazil, with approximately 4,000 cases per year ( Isbister and Fan, 2011 ; Gewehr et al, 2013 ), P. nigriventer venom contains peptides that have therapeutic effects in a range of disease models including chronic pain ( Pedron et al, 2021 ; Cavalli et al, 2022 ), Huntington’s disease ( Joviano-Santos et al, 2022 ), glaucoma ( da Silva et al, 2020 ) and erectile dysfunction ( Nunes da Silva et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics

Cardoso

Walker

King

et al. 2023

Front. Mol. Biosci.

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Introduction: Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer, often referred to as the Brazilian wandering spider, banana spider or “armed” spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models.Methods: In this study, we explored the neuroactivity and molecular diversity of P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor.Results: Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined.Discussion: Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics

Cardoso

Walker

King

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…This has been demonstrated for numerous spider venoms (Smith et al, 2015;Cardoso and Lewis, 2018;2019), including the venom of the infamous South American ctenid spider Phoneutria nigriventer , often referred as Brazilian wandering spider, banana spider or “armed” spider (Peigneur et al, 2018). Besides its clinical relevance due to frequent envenomation cases in Brazil, with approximately 4,000 cases per year (Isbister and Fan, 2011;Gewehr et al, 2013), P. nigriventer venom contains peptides that have therapeutic effects in a range of disease models including chronic pain (Pedron et al, 2021;Cavalli et al, 2022), Huntington’s disease (Joviano-Santos et al, 2022), glaucoma (da Silva et al, 2020) and erectile dysfunction (Nunes da Silva et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Holistic profiling of the venom from the lethal spiderPhoneutria nigriventerby combining high-throughput ion channel screens with venomics

Cardoso

Walker

King

et al. 2022

Preprint

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Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer, often referred to as the Brazilian wandering spider, banana spider or armed spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models. In this study, we explored the neuroactivity and molecular diversity P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor. Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined. Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggests that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.

show abstract

Systemic, Intrathecal, and Intracerebroventricular Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512–2 Toxin in Persistent Pain Models

Cited by 2 publications

References 98 publications

Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics

Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics

Holistic profiling of the venom from the lethal spiderPhoneutria nigriventerby combining high-throughput ion channel screens with venomics

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