Curcumin Ameliorates Memory Decline via Inhibiting BACE1 Expression and β-Amyloid Pathology in 5×FAD Transgenic Mice

Mol Neurobiol. 2017 Apr;54(3):1967-1977. doi: 10.1007/s12035-016-9802-9. Epub 2016 Feb 24.

Abstract

Alzheimer's disease (AD) is the most common dementia and the trigger of its pathological cascade is widely believed to be the overproduction and accumulation of β-amyloid protein (Aβ) in the affected brain. However, effective AD remedies are still anxiously awaited. Recent evidence suggests that curcumin may be a potential agent for AD treatment. In this study, we used 5×FAD transgenic mice as an AD model to investigate the effects of curcumin on AD. Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression, preventing synaptic degradation, and improving spatial learning and memory impairment of 5×FAD mice. These findings suggest that curcumin is a potential candidate for AD treatment.

Keywords: Alzheimer’s disease (AD); Curcumin; β-Amyloid protein (Aβ); β-Site amyloid precursor protein cleavage enzyme 1 (BACE1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / biosynthesis*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / biosynthesis*
  • Aspartic Acid Endopeptidases / genetics
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Gene Expression
  • Male
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism*
  • Memory Disorders / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism*

Substances

  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse
  • Curcumin