title: Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress.
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.
authors: Department of Medical Elementology and Toxicology (Fund for the Improvement of Science and Technology Sponsored by DST and Special Assistance Programme Sponsored by UGC), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
authors: Andleeb
authors: A
authors: Khan
authors: Kumar
authors: K
authors: Vaibhav
authors: Hayate
authors: H
authors: Javed
authors: Mohd Moshahid
authors: MM
authors: Khan
authors: Rizwana
authors: R
authors: Tabassum
authors: Md Ejaz
authors: ME
authors: Ahmed
authors: Pallavi
authors: P
authors: Srivastava
authors: Gulrana
authors: G
authors: Khuwaja
authors: Farah
authors: F
authors: Islam
authors: Mohd Saeed
authors: MS
authors: Siddiqui
authors: Mohammed M
authors: MM
authors: Safhi
authors: Mohammed M
authors: MM
authors: Shafi
authors: Fakhrul
authors: F
authors: Islam
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016227:Benzoquinones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017392:Thiobarbituric Acid Reactive Substances; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D000110:Acetylcholinesterase; C003466:thymoquinone