Protective effect of quercetin in primary neurons against Aβ(1-42): relevance to Alzheimer's disease

Mubeen Ahmad Ansari, Hafiz Mohammad Abdul, Gururaj Joshi, Wycliffe O. Opii, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

359 Scopus citations

Abstract

Quercetin, a flavonoid found in various foodstuffs, has antioxidant properties and increases glutathione (GSH) levels and antioxidant enzyme function. Considerable attention has been focused on increasing the intracellular GSH levels in many diseases, including Alzheimer's disease (AD). Amyloid beta-peptide [Aβ(1-42)], elevated in AD brain, is associated with oxidative stress and neurotoxicity. We aimed to investigate the protective effects of quercetin on Aβ(1-42)-induced oxidative cell toxicity in cultured neurons in the present study. Decreased cell survival in neuronal cultures treated with Aβ(1-42) correlated with increased free radical production measured by dichlorofluorescein fluorescence and an increase in protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (protein-bound 4-hydroxy-2-nonenal). Pretreatment of primary hippocampal cultures with quercetin significantly attenuated Aβ(1-42)-induced cytotoxicity, protein oxidation, lipid peroxidation and apoptosis. A dose-response study suggested that quercetin showed protective effects against Aβ(1-42) toxicity by modulating oxidative stress at lower doses, but higher doses were not only non-neuroprotective but also toxic. These findings provide motivation to test the hypothesis that quercetin may provide a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases.

Original languageEnglish
Pages (from-to)269-275
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume20
Issue number4
DOIs
StatePublished - Apr 2009

Bibliographical note

Funding Information:
This research was supported in part by NIH Grants AG-10836 and AG-05119.

Keywords

  • Alzheimer's disease
  • Aβ(1-42)
  • Neuroprotection
  • Oxidative stress
  • Quercetin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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