Lipid alterations in human frontal cortex in ALS-FTLD-TDP43 proteinopathy spectrum are partly related to peroxisome impairment.
fatty acid profiling
human frontal cortex
lipidomics
peroxisomes
plasmalogens
transcriptomics
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
26
10
2020
received:
21
08
2020
accepted:
13
12
2020
pubmed:
18
12
2020
medline:
23
2
2022
entrez:
17
12
2020
Statut:
ppublish
Résumé
Peroxisomes play a key role in lipid metabolism, and peroxisome defects have been associated with neurodegenerative diseases such as X-adrenoleukodystrophy and Alzheimer's disease. This study aims to elucidate the contribution of peroxisomes in lipid alterations of area 8 of the frontal cortex in the spectrum of TDP43-proteinopathies. Cases of frontotemporal lobar degeneration-TDP43 (FTLD-TDP), manifested as sporadic (sFTLD-TDP) or linked to mutations in various genes including expansions of the non-coding region of C9ORF72 (c9FTLD), and of sporadic amyotrophic lateral sclerosis (sALS) as the most common TDP43 proteinopathies, were analysed. We used transcriptomics and lipidomics methods to define the steady-state levels of gene expression and lipid profiles. Our results show alterations in gene expression of some components of peroxisomes and related lipid pathways in frontal cortex area 8 in sALS, sFTLD-TDP and c9FTLD. Additionally, we identify a lipidomic pattern associated with the ALS-FTLD-TDP43 proteinopathy spectrum, notably characterised by down-regulation of ether lipids and acylcarnitine among other lipid species, as well as alterations in the lipidome of each phenotype of TDP43 proteinopathy, which reveals commonalities and disease-dependent differences in lipid composition. Globally, lipid alterations in the human frontal cortex of the ALS-FTLD-TDP43 proteinopathy spectrum, which involve cell membrane composition and signalling, vulnerability against cellular stress and possible glucose metabolism, are partly related to peroxisome impairment.
Identifiants
pubmed: 33332650
doi: 10.1111/nan.12681
pmc: PMC8248144
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
544-563Informations de copyright
© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
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