Lipid alterations in human frontal cortex in ALS-FTLD-TDP43 proteinopathy spectrum are partly related to peroxisome impairment.
Neuropathol Appl Neurobiol
; 47(4): 544-563, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33332650
ABSTRACT
AIM:
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.METHODS:
We used transcriptomics and lipidomics methods to define the steady-state levels of gene expression and lipid profiles.RESULTS:
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.CONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peroxissomos
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Metabolismo dos Lipídeos
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Proteinopatias TDP-43
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Lobo Frontal
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Esclerose Lateral Amiotrófica
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Espanha