Contribution of DNA/RNA Structures Formed by Expanded CGG/CCG Repeats Within the FMR1 Locus in the Pathogenesis of Fragile X‐Associated Disorders DOI Creative Commons
Izabela Broniarek, Daria Niewiadomska, Krzysztof Sobczak

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(6)

Published: Nov. 1, 2024

Repeat expansion disorders (REDs) encompass over 50 inherited neurological and are characterized by the of short tandem nucleotide repeats beyond a specific repeat length. Particularly intriguing among these multiple fragile X-associated (FXds), which arise from an CGG in 5' untranslated region FMR1 gene. Despite arising expansions same gene, clinical manifestations FXds vary widely, encompassing developmental delays, parkinsonism, dementia, increased risk infertility. also exhibit molecular mechanisms observed other REDs, that is, gene- protein-loss-of-function RNA- protein-gain-of-function. The heterogeneity phenotypes pathomechanisms results different lengths tract. As number increases, structures formed RNA DNA fragments containing change significantly, contributing to diversity FXd mechanisms. In this review, we discuss role expanded driving pathogenesis how genetic instability is mediated complex interplay between transcription, replication, repair. We therapeutic strategies, including small molecules, antisense oligonucleotides, CRISPR-Cas systems, target toxic involved development FXds.

Language: Английский

iTBS Improves Behavioral Abnormalities and Synaptic Defects in Fmr1 KO Rats by Regulating the Autophagy Pathway DOI
S. M. Wu, Zhifeng Deng,

Yaqing Zhao

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Contribution of DNA/RNA Structures Formed by Expanded CGG/CCG Repeats Within the FMR1 Locus in the Pathogenesis of Fragile X‐Associated Disorders DOI Creative Commons
Izabela Broniarek, Daria Niewiadomska, Krzysztof Sobczak

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(6)

Published: Nov. 1, 2024

Repeat expansion disorders (REDs) encompass over 50 inherited neurological and are characterized by the of short tandem nucleotide repeats beyond a specific repeat length. Particularly intriguing among these multiple fragile X-associated (FXds), which arise from an CGG in 5' untranslated region FMR1 gene. Despite arising expansions same gene, clinical manifestations FXds vary widely, encompassing developmental delays, parkinsonism, dementia, increased risk infertility. also exhibit molecular mechanisms observed other REDs, that is, gene- protein-loss-of-function RNA- protein-gain-of-function. The heterogeneity phenotypes pathomechanisms results different lengths tract. As number increases, structures formed RNA DNA fragments containing change significantly, contributing to diversity FXd mechanisms. In this review, we discuss role expanded driving pathogenesis how genetic instability is mediated complex interplay between transcription, replication, repair. We therapeutic strategies, including small molecules, antisense oligonucleotides, CRISPR-Cas systems, target toxic involved development FXds.

Language: Английский

Citations

0