Self-assembling nanofibers improve cognitive impairment in a transgenic mice model of Alzheimer's disease

Neurosci Lett. 2013 Nov 27:556:63-8. doi: 10.1016/j.neulet.2013.09.063. Epub 2013 Oct 5.

Abstract

The peptide amphiphile (PA) with a laminin epitope IKVAV (IKVAV-PA) can be trigged into three-dimensional nanostructures in vivo. Application of IKVAV-PA to the injured spinal cord resulted in significant functional improvement in rodents with remarkable axonal regeneration at the lesion site. Here we showed that injection of IKVAV-PA into the hippocampus of a transgenic (Tg) mice model of Alzheimer's disease (AD) significantly improved cognitive impairment, accompanied by an enhanced neurogenesis in the hippocampus. Further examination demonstrated that IKVAV-PA injections also significantly reduced the levels of soluble Aβ1-40, Aβ1-42, and amyloid-beta (Aβ) plaques in these brains. Our data suggest that IKVAV-PA may serve as a potential therapeutic intervention for the learning and memory losses in AD.

Keywords: Alzheimer's disease; Amyloid-beta; Cognition; Neurogenesis; Peptide amphiphile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Differentiation
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Laminin / therapeutic use*
  • MAP Kinase Signaling System
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nanofibers / therapeutic use*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / pathology
  • Neurogenesis
  • Neurons / drug effects
  • Neurons / pathology
  • Peptide Fragments / metabolism
  • Peptide Fragments / therapeutic use*
  • Plaque, Amyloid / pathology

Substances

  • Amyloid beta-Peptides
  • Laminin
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • isoleucyl-lysyl-valyl-alanyl-valine
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3