Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae) in rats undergoing intrahippocampal NMDA microinjection

Fachim, Helene; Mortari, Márcia Renata; Gobbo-Netto, Leonardo; Santos, Wagner Ferreira dos

doi:10.4103/0973-1296.160450

Cited by 10 publications

(3 citation statements)

References 30 publications

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“…In some other studies, the Parawixin protein family extracted from the Parawixia bistriata spider was examined. Some of these family proteins (Parawixin1, Parawixin2, and Parawixin10) are NMDA antagonists with neuroprotective effects in both in vitro and in vivo models of excitotoxicity ( Fontana et al, 2007 ; Fachim et al, 2015 ; Liberato et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The synergic effects of presynaptic calcium channel antagonists purified from spiders on memory elimination of glutamate-induced excitotoxicity in the rat hippocampus trisynaptic circuit

Keimasi,

Salehifard,

Mirshah Jafar Esfahani

et al. 2023

Front. Mol. Biosci.

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The hippocampus is a complex area of the mammalian brain and is responsible for learning and memory. The trisynaptic circuit engages with explicit memory. Hippocampal neurons express two types of presynaptic voltage-gated calcium channels (VGCCs) comprising N and P/Q-types. These VGCCs play a vital role in the release of neurotransmitters from presynaptic neurons. The chief excitatory neurotransmitter at these synapses is glutamate. Glutamate has an essential function in learning and memory under normal conditions. The release of neurotransmitters depends on the activity of presynaptic VGCCs. Excessive glutamate activity, due to either excessive release or insufficient uptake from the synapse, leads to a condition called excitotoxicity. This pathological state is common among all neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Under these conditions, glutamate adversely affects the trisynaptic circuitry, leading to synaptic destruction and loss of memory and learning performance. This study attempts to clarify the role of presynaptic VGCCs in memory performance and reveals that modulating the activity of presynaptic calcium channels in the trisynaptic pathway can regulate the excitotoxic state and consequently prevent the elimination of neurons and synaptic degradation. All of these can lead to an improvement in learning and memory function. In the current study, two calcium channel blockers—omega-agatoxin-Aa2a and omega-Lsp-IA—were extracted, purified, and identified from spiders (Agelena orientalis and Hogna radiata) and used to modulate N and P/Q VGCCs. The effect of omega-agatoxin-Aa2a and omega-Lsp-IA on glutamate-induced excitotoxicity in rats was evaluated using the Morris water maze task as a behavioral test. The local expression of synaptophysin (SYN) was visualized for synaptic quantification using an immunofluorescence assay. The electrophysiological amplitudes of the field excitatory postsynaptic potentials (fEPSPs) in the input-output and LTP curves of the mossy fiber and Schaffer collateral circuits were recorded. The results of our study demonstrated that N and P/Q VGCC modulation in the hippocampus trisynaptic circuit of rats with glutamate-induced excitotoxicity dysfunction could prevent the destructive consequences of excitotoxicity in synapses and improve memory function and performance.

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Section: Discussionmentioning

confidence: 99%

The synergic effects of presynaptic calcium channel antagonists purified from spiders on memory elimination of glutamate-induced excitotoxicity in the rat hippocampus trisynaptic circuit

Keimasi,

Salehifard,

Mirshah Jafar Esfahani

et al. 2023

Front. Mol. Biosci.

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“…Parawixin10, a compound isolated from Parawixia bistriata spider venom, is a non-selective PAM of EAAT1 and EAAT2, with in vitro neuroprotective properties [47] and in vivo neuroprotection in epilepsy models of intrahippocampal injection of NMDA [48], kainic acid and pentylenetetrazol (PTZ) [49], and pilocarpine [50]. These studies served as proof of concept that EAAT1-2 PAMs may offer neuroprotection and anticonvulsant properties.…”

Section: Epilepsymentioning

confidence: 96%

Glutamate transporters in health and disease

L. Reeb,

K. Gill,

Temmermand

et al. 2024

Two Sides of the Same Coin - Glutamate in Health and Disease [Working Title]

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Glutamate transporters, or excitatory amino acid transporters (EAATs), are key proteins that regulate the excitatory tone in the central nervous system (CNS) by clearing synaptic glutamate, maintaining extracellular glutamate concentrations low enough to prevent receptor desensitization and/or glutamate-mediated excitotoxicity. Dysregulation of the function and/or expression of the EAATs is implicated in several diseases, including epilepsy, stroke, traumatic brain injury, drug abuse disorders, neurodegenerative disorders, and neuropathic pain, among others. In this chapter, we will discuss the regulatory mechanisms of EAATs in health and disease states. We will discuss post-translational modifications, trafficking deficits, reverse transport, and other regulatory processes. We will also discuss current approaches on potential therapeutic strategies targeting these transporters for many neuropsychiatric diseases.

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“…Using a rat glaucoma model based on ischemia/reperfusion of retina, it was shown that the compound called FrPbAII promoted neuroprotection of the retinal cell layers and was also capable of crossing the BBB ( Beleboni et al, 2006 ). Parawixin 1, another compound purified from the venom of Parawixia bistriata , similarly to FrPbAII, has neuroprotective effects demonstrated on retina ischemia/reperfusion glaucoma models ( Fachim et al, 2015 ). Also from Parawixia bistriata venom, PbTx1.2.3, has protected neurons from degeneration in the ischemia/reperfusion retina model, probably through anti excitotoxic activity ( Fontana et al, 2003 ).…”

Section: Animal Toxins To Treat Neurodegenerative Diseasesmentioning

confidence: 99%

Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases

et al. 2018

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Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death. Venoms are fruitful natural sources of new molecules, which have been relentlessly enhanced by evolution through natural selection. Several studies indicate that venom components can exhibit selectivity and affinity for a wide variety of targets in mammalian systems. For instance, an expressive number of natural peptides identified in venoms from animals, such as snakes, scorpions, bees, and spiders, were shown to lessen inflammation, regulate glutamate release, modify neurotransmitter levels, block ion channel activation, decrease the number of protein aggregates, and increase the levels of neuroprotective factors. Thus, these venom components hold potential as therapeutic tools to slow or even halt neurodegeneration. However, there are many technological issues to overcome, as venom peptides are hard to obtain and characterize and the amount obtained from natural sources is insufficient to perform all the necessary experiments and tests. Fortunately, technological improvements regarding heterologous protein expression, as well as peptide chemical synthesis will help to provide enough quantities and allow chemical and pharmacological enhancements of these natural occurring compounds. Thus, the main focus of this review is to highlight the most promising studies evaluating animal toxins as therapeutic tools to treat a wide variety of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, brain ischemia, glaucoma, amyotrophic lateral sclerosis, and multiple sclerosis.

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Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae) in rats undergoing intrahippocampal NMDA microinjection

Cited by 10 publications

References 30 publications

The synergic effects of presynaptic calcium channel antagonists purified from spiders on memory elimination of glutamate-induced excitotoxicity in the rat hippocampus trisynaptic circuit

The synergic effects of presynaptic calcium channel antagonists purified from spiders on memory elimination of glutamate-induced excitotoxicity in the rat hippocampus trisynaptic circuit

Glutamate transporters in health and disease

Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases

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