The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal survival by blocking NMDA receptors. (15th March 2016)

• Record Type: Journal Article
• Authors: Silva, Flavia R.; Batista, Edleusa M.L.; Gomez, Marcus V.; Kushmerick, Christopher; Da Silva, Juliana F.; Cordeiro, Marta N.; Vieira, Luciene B.; Ribeiro, Fabiola M.
• Is Part Of: Toxicon. Volume 112(2016)
• Page Start: 16
• Page End: 21
• Publication Date: 2016-03-15
• Subjects: NMDA receptors -- Excitotoxicity -- PnTx4-5-5 -- Amyloid β peptide -- Neuroprotection; NMDAR N-methyl-d-aspartate receptor -- DIV days in vitro -- ANOVA analysis of variance -- HD Huntington's disease -- AD Alzheimer's disease -- PD Parkinson's disease -- DNQX 6, 7-dinitroquinoxaline-2, 3-dione; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2016.01.056
• Languages: English
• ISSNs: 0041-0101

Abstract

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 PnTx4-5-5 is a potential neuroprotective drug. Highlights: PnTx4-5-5 is a new tool to block NDMAR currents. PnTx4-5-5 protects neurons from both glutamate and amyloid β peptide. PnTx4-5-5 promotes survival of neurons from a mouse model of Huntington's disease.