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Neuroprotective Role of a Novel Copper Chelator against A? 42 Induced Neurotoxicity.

ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disease and associated with the extracellular deposits of amyloid- ? peptide in hippocampus region. Metal ions like Cu, Fe and Zn are known to associate with the amyloid beta (A ? ) at high concentration and interaction of these ions with soluble and aggregated forms of A ? peptide help in development of AD. Here we showed Cu mediated neurotoxicity in the eye tissues of transgenic Drosophila expressing human amyloid ? and its rescue through a novel Cu chelator. In this context, we have synthesised and characterized the compound L 2,6-Pyridinedicarboxylic acid, 2,6-bis[2-[(4-carboxyphenyl) methylene] hydrazide] by Mass spectra (MS) and Elemental analysis (EA). The Cu chelation potential of the compound L is tested in vivo in Drosophila. Oral administration of Copper to the transgenic larvae resulted in severe degeneration in eye tissues, which was rescued by the supplementation of compound L. The levels of anti-oxidant markers like SOD and MDA were measured in compound L treated flies and found a significant rescue (P < 0.001). Further rescue of the eye degeneration phenotypes as revealed by SEM affirm the role of copper in A ? toxicity. Hence, use of compound L, an amidoamine derivative, could be a possible therapeutic measure for A ? induced neurotoxicity.

SUBMITTER: Singh SK

PROVIDER: S-EPMC3789492 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Neuroprotective Role of a Novel Copper Chelator against Aβ 42 Induced Neurotoxicity.

Singh Sandeep Kumar SK Sinha Priti P Mishra L L Srikrishna S S

International journal of Alzheimer's disease 20130918

Alzheimer's disease (AD) is a progressive neurodegenerative disease and associated with the extracellular deposits of amyloid- β peptide in hippocampus region. Metal ions like Cu, Fe and Zn are known to associate with the amyloid beta (A β ) at high concentration and interaction of these ions with soluble and aggregated forms of A β peptide help in development of AD. Here we showed Cu mediated neurotoxicity in the eye tissues of transgenic Drosophila expressing human amyloid β and its rescue thr ...[more]

PMID: 24159420

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Project description:Heavy metal exposure, in lead (Pb) particularly, is associated with severe neuronal impairment though oxidative stress mediated by reactive oxygen species, and antioxidants may be used to abolish these adverse effects. This study investigated the potential neuroprotective role of coenzyme Q10 (CoQ10) against lead acetate (PbAc)-induced neurotoxicity. Twenty-eight male Wistar albino rats were divided into four equal groups (n = 7) and treated as follows: the control group was injected with physiological saline (0.9% NaCl); the CoQ10 group was injected with CoQ10 (10 mg/kg); PbAc group was injected with PbAc (20 mg/kg); PbAc + CoQ10 group was injected first with PbAc, and after 1 h with CoQ10. All groups were injected intraperitoneally for seven days. PbAc significantly increased cortical lipid peroxidation, nitrate/nitrite levels, and inducible nitric oxide synthase expression, and decreased glutathione content, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activity and mRNA expression, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and homoxygenase-1 (HO-1) expression. PbAc also promoted the secretion of interleukin-1ß and tumor necrosis factor-?, inhibited interleukin-10 production, triggered the activation of pro-apoptotic proteins, and suppressed anti-apoptotic proteins. Additionally, PbAc increased the cortical levels of serotonin, dopamine, norepinephrine, GABA, and glutamate, and decreased the level of ATP. However, treatment with CoQ10 rescued cortical neurons from PbAc-induced neurotoxicity by restoring the balance between oxidants and antioxidants, activating the Nrf2/HO-1 pathway, suppressing inflammation, inhibiting the apoptotic cascade, and modulating cortical neurotransmission and energy metabolism. Altogether, our findings indicate that CoQ10 has beneficial effects against PbAc-induced neuronal damage through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.

Dataset Information

Neuroprotective Role of a Novel Copper Chelator against A? 42 Induced Neurotoxicity.

Publications

Neuroprotective Role of a Novel Copper Chelator against Aβ 42 Induced Neurotoxicity.

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