Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.

Published

Journal Article

Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice.

Full Text

Duke Authors

Cited Authors

  • Matak, P; Matak, A; Moustafa, S; Aryal, DK; Benner, EJ; Wetsel, W; Andrews, NC

Published Date

  • March 29, 2016

Published In

Volume / Issue

  • 113 / 13

Start / End Page

  • 3428 - 3435

PubMed ID

  • 26929359

Pubmed Central ID

  • 26929359

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1519473113

Language

  • eng

Conference Location

  • United States