Insights into the identification of a molecular signature for amyotrophic lateral sclerosis exploiting integrated microRNA profiling of iPSC-derived motor neurons and exosomes.
ALS
CSF
Exosomes
Motor neurons
miRNA
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
14 Mar 2022
14 Mar 2022
Historique:
received:
05
11
2021
accepted:
21
02
2022
revised:
18
02
2022
entrez:
14
3
2022
pubmed:
15
3
2022
medline:
18
3
2022
Statut:
epublish
Résumé
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by progressive degeneration of motor neurons (MNs). Most cases are sporadic, whereas 10% are familial. The pathological mechanisms underlying the disease are partially understood, but it is increasingly being recognized that alterations in RNA metabolism and deregulation of microRNA (miRNA) expression occur in ALS. In this study, we performed miRNA expression profile analysis of iPSC-derived MNs and related exosomes from familial patients and healthy subjects. We identified dysregulation of miR-34a, miR-335 and miR-625-3p expression in both MNs and exosomes. These miRNAs regulate genes and pathways which correlate with disease pathogenesis, suggesting that studying miRNAs deregulation can contribute to deeply investigate the molecular mechanisms underlying the disease. We also assayed the expression profile of these miRNAs in the cerebrospinal fluid (CSF) of familial (fALS) and sporadic patients (sALS) and we identified a significant dysregulation of miR-34a-3p and miR-625-3p levels in ALS compared to controls. Taken together, all these findings suggest that miRNA analysis simultaneously performed in different human biological samples could represent a promising molecular tool to understand the etiopathogenesis of ALS and to develop new potential miRNA-based strategies in this new propitious therapeutic era.
Identifiants
pubmed: 35286466
doi: 10.1007/s00018-022-04217-1
pii: 10.1007/s00018-022-04217-1
pmc: PMC8921154
doi:
Substances chimiques
MIRN34 microRNA, human
0
MIRN625 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
189Subventions
Organisme : Fondazione Italiana di Ricerca per la SLA, AriSLA
ID : smallRNALS
Organisme : Fondazione Regionale per la Ricerca Biomedica, FRRB
ID : TransALS
Organisme : Italian Ministry of Health
ID : Ricerca Corrente 2020 RC245
Organisme : E-Rare3 JTC2018
ID : Integrals
Organisme : Italian Ministry of Health
ID : RF-2013-02355764
Organisme : The E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders
ID : senior clinical investigatorship of FWO-Vlaanderen
Informations de copyright
© 2022. The Author(s).
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