R-LOOPs on Short Tandem Repeat Expansion Disorders in Neurodegenerative Diseases.
DNA damage
Neurodegenerative diseases
R-LOOPs
Short tandem repeat expansion disorders
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
16
05
2023
accepted:
24
07
2023
medline:
21
11
2023
pubmed:
4
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
Expansions of short tandem repeats (STRs) have been found to be present in more than 50 diseases and have a close connection with neurodegenerative diseases. Transcriptional silencing and R-LOOP formation, RNA-mediated sequestration of RNA-binding proteins (RBPs), gain-of-function (GOF) proteins containing expanded repeats, and repeat-associated non-AUG (RAN) translation of toxic repeat peptides are some potential molecular mechanisms underlying STR expansion disorders. R-LOOP, a byproduct of transcription, is a three-stranded nucleic acid structure with abnormal accumulation that participates in the pathogenesis of STR expansion disorders by inducing DNA damage and genome instability. R-LOOPs can engender a series of DNA damage, such as DNA double-strand breaks (DSBs), single-strand breaks (SSBs), DNA recombination, or mutations in the DNA replication, transcription, or repair processes. In this review, we provide an in-depth discussion of recent advancements in R-LOOP and systematically elaborate on its genetic destabilizing effects in several neurodegenerative diseases. These molecular mechanisms will provide novel targets for drug design and therapeutic upgrading of these devastating diseases.
Identifiants
pubmed: 37540313
doi: 10.1007/s12035-023-03531-4
pii: 10.1007/s12035-023-03531-4
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
7185-7195Subventions
Organisme : Excellent Youth Foundation of Hunan Province
ID : 2023JJ10098
Organisme : National Natural Science Foundation of China
ID : 82071437
Organisme : Natural Science Foundation of Hunan Province
ID : 2021JJ3115
Organisme : National Key Research and Development Program of China
ID : 2021YFC2501200
Organisme : the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)
ID : 2021KFJJ10
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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