Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: beneficial effect of docosahexaenoic acid on cognitive decline in Alzheimer's disease

J Pharmacol Sci. 2011;116(2):150-62. doi: 10.1254/jphs.10r33fm. Epub 2011 May 21.


Docosahexaenoic acid (DHA, C22:6 n-3), the most abundant n-3 polyunsaturated fatty acid in the brain, is essential for brain growth and development. Recent evidence has indicated the potential health benefits of DHA for managing Alzheimer's disease (AD). For example, dietary administration of DHA considerably protects against and ameliorates the impairment of learning ability in amyloid-beta (Aβ)(1-40)-infused AD-model rats, with concurrent increases in DHA levels and decreases in the levels of lipid peroxide and reactive oxygen species in the cortico-hippocampal tissues. In addition, dietary DHA helps in eliminating the amyloid burden from the brains of AD-model rats. In vitro studies have revealed that DHA substantially inhibits Aβ fibrillation. Furthermore, DHA reduces amyloid-induced toxicity in cell culture. These in vitro data support the hypothesis that DHA can ameliorate the cognitive deficits of AD in vivo by limiting Aβ polymerization in the brains. Therefore, it might be a useful therapeutic agent to prevent and/or delay cognitive impairment in mild cases of AD.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Animals
  • Brain / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Disease Models, Animal
  • Docosahexaenoic Acids / deficiency
  • Docosahexaenoic Acids / pharmacology
  • Docosahexaenoic Acids / therapeutic use*
  • Humans
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Rats


  • Neuroprotective Agents
  • Docosahexaenoic Acids