Osthole decreases beta amyloid levels through up-regulation of miR-107 in Alzheimer's disease

Neuropharmacology. 2016 Sep:108:332-44. doi: 10.1016/j.neuropharm.2016.04.046. Epub 2016 Apr 30.

Abstract

Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). Although osthole has been shown to neuroprotective activity in AD, the exact molecular mechanism of its neuroprotective effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of AD development and progression, indicating that targeting miRNAs could be a novel strategy to treat AD. In the current study, we investigated whether a natural coumarin derivative osthole could up-regulate miR-107, resulting in facilitating the cells survival, reducing LDH leakage, inhibiting apoptosis and reducing beta amyloid (Aβ) production in AD. We found that osthole treatment significantly up-regulate miR-107 expression and inhibited BACE1, one of the targets of miR-107. Administration of osthole to APP/PS1 transgenic mice resulted in a significant improvement in learning and memory function, which was associated with a significant a decrease in Aβ in the hippocampal and cortex region of the brain. Our findings demonstrated that osthole plays a neuroprotective activity role in part through up-regulate miR-107 in AD.

Keywords: Alzheimer’s disease; Aβ; BACE1; Osthole; miRNA-107.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / biosynthesis*
  • Animals
  • Animals, Newborn
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Coumarins / pharmacology
  • Coumarins / therapeutic use*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / biosynthesis*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*

Substances

  • Amyloid beta-Peptides
  • Coumarins
  • MIRN107 microRNA, mouse
  • MicroRNAs
  • Neuroprotective Agents
  • osthol