Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy

Nat Nanotechnol. 2017 Oct;12(10):1006-1014. doi: 10.1038/nnano.2017.133. Epub 2017 Jul 17.

Abstract

Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes. In vivo dopaminergic neuron reprogramming by EMF stimulation of AuNPs efficiently and non-invasively alleviated symptoms in mouse Parkinson's disease models. This study provides a proof of principle for EMF-based in vivo lineage conversion as a potentially viable and safe therapeutic strategy for the treatment of neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Cell Line
  • Cellular Reprogramming / drug effects*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • Electromagnetic Fields*
  • Enzyme Activation / drug effects
  • Gold / chemistry
  • Gold / pharmacology*
  • Histones / metabolism
  • MPTP Poisoning / metabolism
  • MPTP Poisoning / pathology
  • MPTP Poisoning / therapy*
  • Male
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • Mice
  • Transcription Factors

Substances

  • Brd2 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Transcription Factors
  • Gold