Publications by authors named "Neal Innocent"

Neuropilin tolloid-like 1 (Neto1), is a CUB domain-containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein (APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1(HA) was shown to co-immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1(HA) did not co-immunoprecipitate APP695(FLAG) .

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Two recent reports showed that amyloid precursor protein (APP) may contribute to postsynaptic mechanisms via the regulation of the surface trafficking of excitatory N-methyl-D-aspartate (NMDA) receptors. Here we have investigated the interactions and surface trafficking of NR1-1a/NR2A and NR1-1a/NR2B NMDA receptor subtypes with three APP mutations linked to familial Alzheimer's disease, APP695(Indiana), APP695(London) and APP695(Swedish). Flag-tagged mutated APP695s were generated and shown to be expressed at equivalent levels to wild-type APP695 in mammalian cells.

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Key neuropathological hallmarks of Alzheimer's disease include the accumulation of amyloid-beta (Abeta), disruption of Ca(2+) homeostasis and neurodegeneration. However, the physical nature of the toxic Abeta species is controversial. Here, we examined the effect of aging on acute and chronic actions of Abeta peptides: changes in intracellular Ca(2+) and toxic responses, respectively.

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A recently developed alpha-conotoxin, alpha-conotoxin Arenatus IB-[V11L,V16D] (alpha-CtxArIB[V11L,V16D]) [corrected], is a potent and selective competitive antagonist at rat recombinant alpha7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. alpha7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues, where they are implicated in a variety of functions. In this study, we evaluate this toxin at rat and human native nAChRs.

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Cytoglobin is a recently identified member of the mammalian globin family that is expressed in neuronal cells in the central and peripheral nervous system where its physiological role remains to be determined. In the current study, we demonstrate that a cytoglobin-green fluoresecent protein (GFP) fusion protein when expressed in the human neuronal cell line TE671 has a nuclear localization in a subpopulation of transfected cells (approximately 15%). Furthermore, the cytoglobin-GFP fusion protein but not GFP alone significantly reduced the induction of intracellular reactive oxygen species as assessed by oxidation of the redox-sensitive probe dichlorofluorescein following treatment with non-cytotoxic concentrations of the pro-oxidant Ro19-8022.

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The synthesis of (+/-)-epiquinamide 1 and (+/-)-C(1)-epiepiquinamide 2 based on the use of a Curtius rearrangement to introduce the C(1) amino residue is reported. In a competition binding assay for [(3)H]epibatidine binding to rat brain membranes neither (+/-)-1 nor (+/-)-2 showed any significant level of nicotinic activity.

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