The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal survival by blocking NMDA receptors

Toxicon : Official Journal of the International Society on Toxinology
Flavia R SilvaFabiola M Ribeiro

Abstract

Spider toxins are recognized as useful sources of bioactive substances, showing a wide range of pharmacological effects on neurotransmission. Several spider toxins have been identified biochemically and some of them are specific glutamate receptors antagonists. Previous data indicate that PnTx4-5-5, a toxin isolated from the spider Phoneutria nigriventer, inhibits the N-methyl-d-aspartate receptor (NMDAR), with little or no effect on AMPA, kainate or GABA receptors. In agreement with these results, our findings in this study show that PnTx4-5-5 reduces the amplitude of NMDAR-mediated EPSCs in hippocampal slices. It is well established that glutamate-mediated excitotoxic neuronal cell death occurs mainly via NMDAR activation. Thus, we decided to investigate whether PnTx4-5-5 would protect against various cell death insults. For that, we used primary-cultured corticostriatal neurons from wild type (WT) mice, as well as from a mouse model of Huntington's disease, BACHD. Our results showed that PnTx4-5-5 promotes neuroprotection of WT and BACHD neurons under the insult of high levels of glutamate. Moreover, the toxin is also able to protect WT neurons against amyloid β (Aβ) peptide toxicity. These results indicate that the toxin Pn...Continue Reading

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Citations

Nov 26, 2016·International Journal of Molecular Sciences·Edilene S SoaresMaria Alice da Cruz-Höfling
Oct 6, 2020·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Lays Fernanda Nunes DouradoArmando da Silva Cunha
Mar 13, 2018·Frontiers in Pharmacology·Jessica M de SouzaFabiola M Ribeiro
Aug 31, 2019·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Camila Franco Batista OliveiraMaria Elena de Lima
May 13, 2020·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Ana Luiza Bittencourt PaivaMarcelo Ribeiro Vasconcelos Diniz
Jul 16, 2020·Toxicon : Official Journal of the International Society on Toxinology·Pedro Santana Sales LauriaLuciana Lyra Casais-E-Silva
Sep 26, 2021·Neuromolecular Medicine·Artur Pałasz, Marek Krzystanek

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