Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice

Neurobiol Aging. 2015 Jan;36(1):201-10. doi: 10.1016/j.neurobiolaging.2014.07.041. Epub 2014 Aug 2.

Abstract

Recent evidence supports the amyloid cascade hypothesis that a pathological change of amyloid β (Aβ) in the brain is an initiating event in Alzheimer's disease (AD). Accordingly, modulating the abnormal Aβ aggregation is considered a potential therapeutic target in AD. Curcumin, a low-molecular-weight polyphenol derived from the well-known curry spice turmeric, has shown favorable effects on preventing or treating AD pathology. The present study investigated the effects of curcumin and 2 novel curcumin derivatives, FMeC1 and FMeC2, on AD pathology in APPswe/PS1dE9 double transgenic mice. Mice fed a chow diet that contained FMeC1 for 6 months showed a reduction in insoluble Aβ deposits and glial cell activity together with reduced cognitive deficits, compared to animals receiving a control diet or with curcumin or FMeC2 in their diet. Both curcumin and FMeC1 modulated the formation of Aβ aggregates; however, only FMeC1 significantly attenuated the cell toxicity of Aβ. These results indicate that FMeC1 may have potential for preventing AD.

Keywords: APP/PS1 transgenic mice; Alzheimer's disease; amyloid-β; curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / metabolism*
  • Cognition
  • Curcumin / administration & dosage
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Targeted Therapy
  • Neuroglia / physiology
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism*
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / prevention & control

Substances

  • Amyloid beta-Peptides
  • Presenilin-1
  • presenilin 1, mouse
  • Curcumin