University of Leicester
Browse

File(s) under permanent embargo

Reason: 12 month embargo on AAM -requested from author

Redox stress and metal dys-homeostasis appear as hallmarks of early prion disease pathogenesis in mice.

journal contribution
posted on 2023-07-11, 11:52 authored by Jereme G Spiers, Hsiao-Jou Cortina Chen, Tiffany L Barry, Julie-Myrtille Bourgognon, Joern R Steinert
Neurodegenerative diseases are associated with a multitude of dysfunctional cellular pathways. One major contributory factor is a redox stress challenge during the development of several protein misfolding conditions including Alzheimer's (AD), Parkinson's disease (PD), and less common conditions such as Creutzfeldt Jakob disease (CJD). CJD is caused by misfolding of the neuronal prion protein and is characterised by a neurotoxic unfolded protein response involving chronic endoplasmic reticulum stress, reduced protein translation and spongiosis leading subsequently to synaptic and neuronal loss. Here we have characterised prion disease in mice to assess redox stress components including nitrergic and oxidative markers associated with neuroinflammatory activation. Aberrant regulation of the homeostasis of several redox metals contributes to the overall cellular redox stress and we have identified altered levels of iron, copper, zinc, and manganese in the hippocampus of prion diseased mice. Our data show that early in disease, there is evidence for oxidative stress in conjunction with reduced antioxidant superoxide dismutase mRNA and protein expression. Moreover, expression of divalent metal transporter proteins was reduced for Atp7b, Atox1, Slc11a2, Slc39a14 at 6-7 weeks but increased for Slc39a14 and Mt1 at 10 weeks of disease. Our data present evidence for a strong pro-oxidant environment and altered redox metal homeostasis in early disease pathology which both may be contributory factors to aggravating this protein misfolding disease.

History

Author affiliation

School of Geography, Geology and the Environment, University of Leicester

Version

  • NA (Not Applicable or Unknown)

Published in

Free radical biology & medicine

Volume

192

Pagination

182 - 190

Publisher

Elsevier BV

issn

0891-5849

eissn

1873-4596

Copyright date

2022

Notes

Deposited in CRIS 13/10/2022

Spatial coverage

United States

Language

eng

Usage metrics

    University of Leicester Publications

    Categories

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC