Abstract |
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(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(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(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(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.
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Authors | Andleeb Khan, Kumar Vaibhav, Hayate Javed, Mohd Moshahid Khan, Rizwana Tabassum, Md Ejaz Ahmed, Pallavi Srivastava, Gulrana Khuwaja, Farah Islam, Mohd Saeed Siddiqui, Mohammed M Safhi, Mohammed M Shafi, Fakhrul Islam |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 369
Issue 1-2
Pg. 55-65
(Oct 2012)
ISSN: 1573-4919 [Electronic] Netherlands |
PMID | 22752387
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- Benzoquinones
- Neuroprotective Agents
- Peptide Fragments
- Thiobarbituric Acid Reactive Substances
- amyloid beta-protein (25-35)
- Nitric Oxide
- Glutathione Peroxidase
- Acetylcholinesterase
- thymoquinone
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Topics |
- Acetylcholinesterase
(metabolism)
- Alzheimer Disease
(drug therapy)
- Amyloid beta-Peptides
(antagonists & inhibitors, toxicity)
- Animals
- Apoptosis
(drug effects)
- Benzoquinones
(administration & dosage)
- Cell Survival
(drug effects)
- Glutathione Peroxidase
(metabolism)
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects, pathology)
- Neuroprotective Agents
(administration & dosage)
- Nitric Oxide
(metabolism)
- Oxidative Stress
(drug effects)
- PC12 Cells
- Peptide Fragments
(antagonists & inhibitors, toxicity)
- Rats
- Thiobarbituric Acid Reactive Substances
(metabolism)
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