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Acai Berry (Euterpe sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress (2023)
Journal Article
ALNasser, M. N., AlSaadi, A. M., Whitby, A., Kim, D. H., Mellor, I. R., & Carter, W. G. (2023). Acai Berry (Euterpe sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress. Life, 13(4), Article 1019. https://doi.org/10.3390/life13041019

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe... Read More about Acai Berry (Euterpe sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress.

A Sublethal Concentration of Sulfoxaflor Has Minimal Impact on Buff-Tailed Bumblebee (Bombus terrestris) Locomotor Behaviour under Aversive Conditioning (2023)
Journal Article
James, L., Reynolds, A. M., Mellor, I. R., & Davies, T. G. E. (2023). A Sublethal Concentration of Sulfoxaflor Has Minimal Impact on Buff-Tailed Bumblebee (Bombus terrestris) Locomotor Behaviour under Aversive Conditioning. Toxics, 11(3), Article 279. https://doi.org/10.3390/toxics11030279

Pesticide exposure has been cited as a key threat to insect pollinators. Notably, a diverse range of potential sublethal effects have been reported in bee species, with a particular focus on effects due to exposure to neonicotinoid insecticides. Here... Read More about A Sublethal Concentration of Sulfoxaflor Has Minimal Impact on Buff-Tailed Bumblebee (Bombus terrestris) Locomotor Behaviour under Aversive Conditioning.

(−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors (2022)
Journal Article
Richards, D. P., Patel, R. N., Duce, I. R., Khambay, B. P. S., Birkett, M. A., Pickett, J. A., & Mellor, I. R. (2022). (−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors. Molecules, 27(20), Article 7074. https://doi.org/10.3390/molecules27207074

Ladybird beetles (Coleoptera: Coccinellidae) possess strong chemical defences that are secreted in response to stress and are also found on the coating of eggs, which are rich in alkaloids that are responsible for their toxicity to other species. Rec... Read More about (−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors.

A Preliminary Assessment of the Nutraceutical Potential of Acai Berry (Euterpe sp.) as a Potential Natural Treatment for Alzheimer's Disease (2022)
Journal Article
AL Nasser, M. N., Mellor, I. R., & Carter, W. G. (2022). A Preliminary Assessment of the Nutraceutical Potential of Acai Berry (Euterpe sp.) as a Potential Natural Treatment for Alzheimer's Disease. Molecules, 27(15), Article 4891. https://doi.org/10.3390/molecules27154891

Alzheimer's disease (AD) is characterised by progressive neuronal atrophy and the loss of neuronal function as a consequence of multiple pathomechanisms. Current AD treatments primarily operate at a symptomatic level to treat a cholinergic deficiency... Read More about A Preliminary Assessment of the Nutraceutical Potential of Acai Berry (Euterpe sp.) as a Potential Natural Treatment for Alzheimer's Disease.

Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review (2022)
Journal Article
Al-Nasser, M. N., Mellor, I. R., & Carter, W. G. (2022). Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review. Brain Sciences, 12(5), Article 577. https://doi.org/10.3390/brainsci12050577

L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investig... Read More about Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review.

Non‐canonical endogenous expression of voltage‐gated sodium channel NaV1.7 subtype by the TE671 rhabdomyosarcoma cell line (2022)
Journal Article
Aziz, M. Y., Mohammed Latif, L., Ngum, N. M., Aziz, M. Y. A., Latif, M. L., Wall, R. J., …Mellor, I. R. (2022). Non‐canonical endogenous expression of voltage‐gated sodium channel NaV1.7 subtype by the TE671 rhabdomyosarcoma cell line. Journal of Physiology, 600(10), 2499-2513. https://doi.org/10.1113/JP283055

Abstract: The human TE671 cell line was originally used as a model of medulloblastoma but has since been reassigned as rhabdomyosarcoma. Despite the characterised endogenous expression of voltage-sensitive sodium currents in these cells, the specific... Read More about Non‐canonical endogenous expression of voltage‐gated sodium channel NaV1.7 subtype by the TE671 rhabdomyosarcoma cell line.

Neuroprotection Against NMDA-Induced Retinal Damage by Philanthotoxin-343 Involves Reduced Nitrosative Stress (2021)
Journal Article
Mohamad, M. H. N., Abu, I. F., Fazel, M. F., Agarwal, R., Iezhitsa, I., Juliana, N., …Franzyk, H. (2021). Neuroprotection Against NMDA-Induced Retinal Damage by Philanthotoxin-343 Involves Reduced Nitrosative Stress. Frontiers in Pharmacology, 12, Article 798794. https://doi.org/10.3389/fphar.2021.798794

N-methyl-D-aspartate receptor (NMDAR) overstimulation is known to mediate neurodegeneration, and hence represents a relevant therapeutic target for neurodegenerative disorders including glaucoma. This study examined the neuroprotective effects of phi... Read More about Neuroprotection Against NMDA-Induced Retinal Damage by Philanthotoxin-343 Involves Reduced Nitrosative Stress.

The Effects of Structural Alterations in the Polyamine and Amino Acid Moieties of Philanthotoxins on Nicotinic Acetylcholine Receptor Inhibition in the Locust, Schistocerca gregaria (2021)
Journal Article
Luck, V. L., Richards, D. P., Shaikh, A. Y., Franzyk, H., & Mellor, I. R. (2021). The Effects of Structural Alterations in the Polyamine and Amino Acid Moieties of Philanthotoxins on Nicotinic Acetylcholine Receptor Inhibition in the Locust, Schistocerca gregaria. Molecules, 26(22), Article 7007. https://doi.org/10.3390/molecules26227007

Alterations in the polyamine and amino acid (tyrosine) moieties of philanthotoxin‐343 (PhTX‐343) were investigated for their effects on the antagonism of nicotinic acetylcholine receptors (nAChRs) isolated from the locust (Schistocerca gregaria) mush... Read More about The Effects of Structural Alterations in the Polyamine and Amino Acid Moieties of Philanthotoxins on Nicotinic Acetylcholine Receptor Inhibition in the Locust, Schistocerca gregaria.

Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity (2020)
Journal Article
Fazel, M. F., Abu, I. F., Mohamad, M. H. N., Agarwal, R., Iezhitsa, I., Bakar, N. S., …Franzyk, H. (2020). Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity. PLoS ONE, 15(7), Article e0236450. https://doi.org/10.1371/journal.pone.0236450

Retinal ganglion cell (RGC) loss and optic neuropathy, both hallmarks of glaucoma, have been shown to involve N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity. This study investigated the neuroprotective effects of Philanthotoxin (PhTX)-... Read More about Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity.

The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster (2020)
Journal Article
Thompson, A. J., Verdin, P. S., Burton, M. J., Davies, T. G., Williamson, M. S., Field, L. M., …Duce, I. R. (2020). The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster. Insect Biochemistry and Molecular Biology, 122, Article 103388. https://doi.org/10.1016/j.ibmb.2020.103388

© 2020 Elsevier Ltd Voltage-gated sodium channels (VGSCs) are a major target site for the action of pyrethroid insecticides and resistance to pyrethroids has been ascribed to mutations in the VGSC gene. VGSCs in insects are encoded by only one gene a... Read More about The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster.

Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities (2019)
Journal Article
Koromina, M., Flitton, M., Blockley, A., Mellor, I. R., & Knight, H. (2019). Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities. Scientific Reports, 9, https://doi.org/10.1038/s41598-019-55635-4

Schizophrenia (Scz), autism spectrum disorder (ASD) and intellectual disability are common complex neurodevelopmental disorders. Kainate receptors (KARs) are ionotropic glutamate ion channels involved in synaptic plasticity which are modulated by aux... Read More about Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities.

Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease (2019)
Journal Article
Rosini, M., Simoni, E., Caporaso, R., Basagni, F., Catanzaro, M., Abu, I. F., …Minarini, A. (2019). Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease. European Journal of Medicinal Chemistry, 180, 111-120. https://doi.org/10.1016/j.ejmech.2019.07.011

N-methyl-d-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trig... Read More about Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease.

Philanthotoxin analogues that selectively inhibit ganglionic nicotinic acetylcholine receptors with exceptional potency (2019)
Journal Article
Kachel, H. S., Franzyk, H., & Mellor, I. R. (2019). Philanthotoxin analogues that selectively inhibit ganglionic nicotinic acetylcholine receptors with exceptional potency. Journal of Medicinal Chemistry, 62(13), 6214-6222. https://doi.org/10.1021/acs.jmedchem.9b00519

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 non-selectively inhibits several excitatory ligand-gated ion channels, and we recently showed that its synthetic analogue... Read More about Philanthotoxin analogues that selectively inhibit ganglionic nicotinic acetylcholine receptors with exceptional potency.

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease (2018)
Journal Article
Furutani, S., Ihara, M., Lees, K., Buckingham, S. D., Partridge, F. A., David, J. A., …Sattelle, D. B. (2018). The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease. International Journal for Parasitology: Drugs and Drug Resistance, 8(2), 350-360. https://doi.org/10.1016/j.ijpddr.2018.06.001

A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGl... Read More about The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease.

A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort (2018)
Journal Article
Koromina, M., Flitton, M., Mellor, I. R., & Knight, H. M. (2019). A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort. World Journal of Biological Psychiatry, 20(5), 393-401. https://doi.org/10.1080/15622975.2017.1417637

Objectives: Cognitive deficits are a common feature of neuropsychiatric disorders. We investigated the relationship between cognitive performance and a deletion allele within GluK4 protective against risk for bipolar disorder, in 1642 individuals fro... Read More about A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort.

Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation (2017)
Journal Article
Simioni, E., Bartolini, M., Abu, I. F., Blockley, A., Gotti, C., Bottegoni, G., …Minarini, A. (in press). Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation. Future Medicinal Chemistry, 9(10), https://doi.org/10.4155/fmc-2017-0039

Background: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active pla... Read More about Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation.

Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition (2016)
Journal Article
Kachel, H. S., Patel, R. N., Franzyk, H., & Mellor, I. R. (2016). Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition. Scientific Reports, 6, https://doi.org/10.1038/srep38116

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and P... Read More about Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition.

Insecticide resistance mediated 1 by an exon skipping event (2016)
Journal Article
Berger, M., Puinean, A. M., Randall, E., Zimmer, C. T., Silva, W. M., Bielza, P., …Bass, C. (2016). Insecticide resistance mediated 1 by an exon skipping event. Molecular Ecology, 25(22), https://doi.org/10.1111/mec.13882

Many genes increase coding capacity by alternate exon usage. The gene encoding the insect nicotinic acetylcholine receptor (nAChR) a6 subunit, target of the bio-insecticide spinosad, is one example of this and expands protein diversity via alternativ... Read More about Insecticide resistance mediated 1 by an exon skipping event.

An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids (2015)
Journal Article
Amey, J. S., O'Reilly, A. O., Burton, M. J., Puinean, A. M., Mellor, I. R., Duce, I. R., …Davies, T. E. (2015). An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids. FEBS Letters, 589(5), 598-607. https://doi.org/10.1016/j.febslet.2015.01.020

We describe the identification in aphids of a unique heterodimeric voltage-gated sodium channel which has an atypical ion selectivity filter and, unusually for insect channels, is highly insensitive to tetrodotoxin. We demonstrate that this channel h... Read More about An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids.

Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor (2014)
Journal Article
Wall, R. J., Fernades, A., Rose, M., Bell, D. R., & Mellor, I. R. (2015). Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor. Environment International, 76, 49-56. https://doi.org/10.1016/j.envint.2014.12.002

The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in... Read More about Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor.