title: The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal survival by blocking NMDA receptors.
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.
authors.affiliation: Department of Biochemistry and Immunology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Flavia R
authors.initials: FR
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Immunology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Edleusa M L
authors.initials: EM
authors.lastname: Batista
authors.affiliation: Department of Neurotransmitters, IEP, Santa Casa, Belo Horizonte, Brazil.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Gomez
authors.affiliation: Department of Physiology and Biophysics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kushmerick
authors.affiliation: Department of Neurotransmitters, IEP, Santa Casa, Belo Horizonte, Brazil.
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Da Silva
authors.affiliation: Fundação Ezequiel Dias, Belo Horizonte, Brazil.
authors.forename: Marta N
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Luciene B
authors.initials: LB
authors.lastname: Vieira
authors.affiliation: Department of Biochemistry and Immunology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: fmribeiro@icb.ufmg.br.
authors.forename: Fabiola M
authors.initials: FM
authors.lastname: Ribeiro
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D060829:Arthropod Proteins / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology / Q000473:pathology; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D060829:Arthropod Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013111:Spider Venoms; C418408:Tx4(5-5) neurotoxin, Phoneutria nigriventer
keywords: Amyloid β peptide; Excitotoxicity; NMDA receptors; Neuroprotection; PnTx4-5-5