Attenuation of A[beta]-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress

Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and compounds that can prevent pathways of Aβ-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) w...

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Published in:Molecular and cellular biochemistry 2012-10, Vol.369 (1-2), p.55
Main Authors: Khan, Andleeb, Vaibhav, Kumar, Javed, Hayate, Moshahid Khan, Mohd, Tabassum, Rizwana, Ahmed, Md Ejaz, Srivastava, Pallavi, Khuwaja, Gulrana, Islam, Farah, Saeed Siddiqui, Mohd, Shafi, Mohammed M, Islam, Fakhrul
Format: Article
Language:English
Subjects:
Alzheimer's disease
Mitochondria
Neurons
Neurotoxicity
Nitric oxide
Oxidative stress
Pathogenesis
Peptides
Phytochemicals
Toxicity
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Summary:Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and compounds that can prevent pathways of Aβ-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) would reduce oxidative stress and mitochondrial dysfunction in differentiated pheochromocytoma (PC 12) cells exposed to Aβ fragment 25-35 (Aβ^sub 25-35^). To test this hypothesis, Aβ was used to induce an in vitro model of AD in differentiated PC 12 cell line of rat. After 24 h of exposure with Aβ^sub 25-35^, a significant reduction in cell viability and mitochondrial membrane potential (MMP) was observed. In addition, a significant elevation in the TBARS content and nitric oxide (NO) and activity of acetylcholine esterase (AChE) was observed which was restored significantly by TQ pretreatment. Furthermore, TQ also ameliorated glutathione and its dependent enzymes (glutathione peroxidase, glutathione reductase) which were depleted by Aβ^sub 25-35^ in PC 12 cells. These results were supported by the immunocytochemical finding that has shown protection of cells by TQ from noxious effects of Aβ^sub 25-35^. These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders including AD.[PUBLICATION ABSTRACT]
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-012-1368-x