Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis
metabolomics
mitochondria dysfunction
muscle
transcriptomics
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
02 Jun 2022
02 Jun 2022
Historique:
received:
20
04
2022
revised:
30
05
2022
accepted:
30
05
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
25
6
2022
Statut:
epublish
Résumé
Diverse biomarkers and pathological alterations have been found in muscle of patients with Amyotrophic lateral sclerosis (ALS), but the relation between such alterations and dysfunction in energetic metabolism remains to be investigated. We established the metabolome of muscle and serum of ALS patients and correlated these findings with the clinical status and pathological alterations observed in the muscle. We obtained data from 20 controls and 17 ALS patients (disease duration: 9.4 ± 6.8 months). Multivariate metabolomics analysis identified a distinct serum metabolome for ALS compared to controls (p-CV-ANOVA < 0.035) and revealed an excellent discriminant profile for muscle metabolome (p-CV-ANOVA < 0.0012). Citramalate was discriminant for both muscle and serum. High lauroylcarnitine levels in muscle were associated with low Forced Vital Capacity. Transcriptomics analysis of key antioxidant enzymes showed an upregulation of SOD3 (p = 0.0017) and GLRX2(1) (p = 0.0022) in ALS muscle. Analysis of mitochondrial enzymatic activity in muscle revealed higher complex II/CS (p = 0.04) and lower LDH (p = 0.03) activity in ALS than in controls. Our study showed, for the first time, a global dysfunction in the muscle of early-stage ALS patients. Furthermore, we identified novel metabolites to be employed as biomarkers for diagnosis and prognosis of ALS patients.
Identifiants
pubmed: 35740329
pii: biomedicines10061307
doi: 10.3390/biomedicines10061307
pmc: PMC9220134
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : ARSLA
ID : METABOMU
Organisme : Fondation Brou de Lauriere
ID : METABOMU
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