Parkinson's disease iron deposition caused by nitric oxide-induced loss of β-amyloid precursor protein

J Neurosci. 2015 Feb 25;35(8):3591-7. doi: 10.1523/JNEUROSCI.3439-14.2015.

Abstract

Elevation of both neuronal iron and nitric oxide (NO) in the substantia nigra are associated with Parkinson's disease (PD) pathogenesis. We reported previously that the Alzheimer-associated β-amyloid precursor protein (APP) facilitates neuronal iron export. Here we report markedly decreased APP expression in dopaminergic neurons of human PD nigra and that APP(-/-) mice develop iron-dependent nigral cell loss. Conversely, APP-overexpressing mice are protected in the MPTP PD model. NO suppresses APP translation in mouse MPTP models, explaining how elevated NO causes iron-dependent neurodegeneration in PD.

Keywords: APP; iron; nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cell Line, Tumor
  • Dopaminergic Neurons / metabolism
  • Female
  • Humans
  • Iron / metabolism*
  • MPTP Poisoning / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism*
  • Parkinson Disease / metabolism*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology

Substances

  • Amyloid beta-Protein Precursor
  • Nitric Oxide
  • Iron