%0 Journal Article
%T Neuroprotective Role of a Novel Copper Chelator against Induced Neurotoxicity
%A Sandeep Kumar Singh
%A Priti Sinha
%A L. Mishra
%A S. Srikrishna
%J International Journal of Alzheimer's Disease
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/567128
%X Alzheimer's disease (AD) is a progressive neurodegenerative disease and associated with the extracellular deposits of amyloid-¦Â peptide in hippocampus region. Metal ions like Cu, Fe and Zn are known to associate with the amyloid beta (A¦Â) at high concentration and interaction of these ions with soluble and aggregated forms of A¦Â peptide help in development of AD. Here we showed Cu mediated neurotoxicity in the eye tissues of transgenic Drosophila expressing human amyloid ¦Â 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 ( ). Further rescue of the eye degeneration phenotypes as revealed by SEM affirm the role of copper in A¦Â toxicity. Hence, use of compound L, an amidoamine derivative, could be a possible therapeutic measure for A¦Â induced neurotoxicity. 1. Introduction Alzheimer¡¯s disease (AD) is the most common cause of dementia in the aging population. It is the major neurodegenerative disease of aging brain, mainly associated with the extracellular deposits of amyloid-¦Â plaques and intracellular neurofibrillary tangles (NFT) in hippocampus region of the brain. Several studies across the globe show a strong association between loss of metal homeostasis and AD. Consequently, the research community is seriously considering the role of various bimetals and environmental metal toxins in progression and clinical outcomes of Alzheimer¡¯s disease and other forms of neurodegenerative disorders. Metals play an important role in Alzheimer¡¯s pathology; heavy metals such as lead, cadmium, and mercury especially are highly neurotoxic and have no other biological functions. However, nowadays, people are mainly focusing on biologically important metals such as iron (Fe), zinc (Zn), and copper (Cu) because their imbalance is related to AD. Earlier studies demonstrated that metals like copper and zinc play a critical role in amyloid beta (A¦Â) aggregation and neurotoxicity [1¨C4]. Metal ions, mainly Cu, Fe, and Zn, have been found to colocalize with the amyloid beta (A¦Â) in high concentrations, and interaction of these
%U http://www.hindawi.com/journals/ijad/2013/567128/