Browse by author
Lookup NU author(s): Dr Christopher Morris
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson’s disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson’s have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood. Here, scanning transmission x-ray microscopy (STXM) is used to probe iron foci in relation to the surrounding ultrastructure in melanised neurons of human substantia nigra from a confirmed Parkinson’s case. In addition to the expected neuromelanin-bound iron, iron deposits are also associated with the edge of the cell nucleolus. Speciation analysis confirms these deposits to be ferric (Fe3+) iron. The function of intranuclear iron in these cells remains unresolved, although both damaging and protective mechanisms are considered. This finding shows that STXM is a powerful label-free tool for the in situ, nanoscale chemical characterisation of both organic and inorganic intracellular components. Future applications are likely to shed new light on incompletely understood biochemical mechanisms, such as metal dysregulation and morphological changes to cell nucleoli, that are important in understanding the pathogenesis of Parkinson’s.
Author(s): Brooks J, Everett J, Hill E, Billimoria K, Morris CM, Sadler PJ, Telling N, Collingwood JF
Publication type: Article
Publication status: Published
Journal: Communications Biology
Year: 2024
Volume: 7
Online publication date: 20/08/2024
Acceptance date: 26/07/2024
Date deposited: 02/09/2024
ISSN (electronic): 2399-3642
Publisher: Springer Nature
URL: https://doi.org/10.1038/s42003-024-06636-1
DOI: 10.1038/s42003-024-06636-1
Data Access Statement: The data that support the findings in this study will be available in the Warwick Research Archive Portal (WRAP) repository at https://wrap. warwick.ac.uk/185993.
PubMed id: 39164395
Altmetrics provided by Altmetric
