Alternative Splicing of ALS Genes: Misregulation and Potential Therapies.
ALS genes
Alternative splicing (AS)
Amyotrophic lateral sclerosis (ALS)
RNA-binding protein (RBP)
Splicing factors
Splicing machinery
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
09
04
2019
accepted:
31
07
2019
pubmed:
7
8
2019
medline:
21
10
2020
entrez:
7
8
2019
Statut:
ppublish
Résumé
Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Parkinson's, Alzheimer's, and Huntington's disease affect a rapidly increasing population worldwide. Although common pathogenic mechanisms have been identified (e.g., protein aggregation or dysfunction, immune response alteration and axonal degeneration), the molecular events underlying timing, dosage, expression, and location of RNA molecules are still not fully elucidated. In particular, the alternative splicing (AS) mechanism is a crucial player in RNA processing and represents a fundamental determinant for brain development, as well as for the physiological functions of neuronal circuits. Although in recent years our knowledge of AS events has increased substantially, deciphering the molecular interconnections between splicing and ALS remains a complex task and still requires considerable efforts. In the present review, we will summarize the current scientific evidence outlining the involvement of AS in the pathogenic processes of ALS. We will also focus on recent insights concerning the tuning of splicing mechanisms by epigenomic and epi-transcriptomic regulation, providing an overview of the available genomic technologies to investigate AS drivers on a genome-wide scale, even at a single-cell level resolution. In the future, gene therapy strategies and RNA-based technologies may be utilized to intercept or modulate the splicing mechanism and produce beneficial effects against ALS.
Identifiants
pubmed: 31385134
doi: 10.1007/s10571-019-00717-0
pii: 10.1007/s10571-019-00717-0
doi:
Substances chimiques
Nerve Tissue Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-14Subventions
Organisme : Progetto Invecchiamento
ID : DSB.AD009.001
Organisme : European Social Fund (Rafforzare l'Occupabilità nel sistema R&S e la nascita di spin off di ricerca in Sicilia)
ID : CIP 2014.IT.05.SFOP.014/3/10.4/9.2.10/0008
Organisme : European Social Fund (Rafforzare l'Occupabilità nel sistema R&S e la nascita di spin off di ricerca in Sicilia)
ID : CUP G67B17000170009
Organisme : Ministero dello Sviluppo Economico
ID : DSB.AD008.456
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