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4-Hydroxyisophthalic acid from Decalepis hamiltonii rescues the neurobehavioral deficit in transgenic Drosophila model of taupathies

Haddadi, Mohammad and Jahromi, Samaneh Reiszadeh and Nongthomba, Upendra and Shivanandappa, T and Ramesh, SR (2016) 4-Hydroxyisophthalic acid from Decalepis hamiltonii rescues the neurobehavioral deficit in transgenic Drosophila model of taupathies. In: NEUROCHEMISTRY INTERNATIONAL, 100 . pp. 78-90.

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Official URL: http://dx.doi.org/10.1016/j.neuint.2016.09.007


Oxidative stress is one of the major etiological factors implicated in pathogenesis of neurodegenerative diseases. Since neurons are more sensitive to oxidative damage there is an increasing interest in developing novel antioxidant therapies, especially herbal preparations due to their safety profile and high efficiency. In this regard, the neuroprotective potential of a novel antioxidant compound, 4-hydroxyisophthalic acid (4-HIPA) isolated from aqueous extract of Decalepis hamiltonii roots was examined using transgenic Drosophila model of taupathy expressing wild-type and mutant forms of 2N4R isoform of human microtubule associated protein tau (MAPT). Taupathy model flies showed cognitive deficits in olfactory memory and deteriorated circadian rhythm of locomotory activities. Administration of 0.1 mg/ml 4-HIPA, markedly enhanced their olfactory memory performance and restored circadian rhythmicity of the transgenic flies locomotory behavior to the normal range. The mechanism of action that underlies 4-HIPA neuroprotection involves enhancement in efficiency of cellular antioxidant defense system by means of elevation in antioxidant enzyme activities and attenuation of oxidative stress. The molecule could positively affect the activity of neurotransmitter enzymes, which in turn enhances neuronal function and ameliorates the Tau-induced neurobehavioral deficits. Our findings showed that 4-HIPA can be considered as a suitable therapeutic candidate for drug development towards treatment of neurodegenerative disorders. (C) 2016 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 04 Jan 2017 04:50
Last Modified: 04 Jan 2017 04:50
URI: http://eprints.iisc.ac.in/id/eprint/55710

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