G-quadruplex DNA and RNA in cellular senescence DOI Creative Commons

Rocio Diaz Escarcega,

Paul R. Marshall, Andrey S. Tsvetkov

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Oct. 9, 2024

Normal cells divide, are damaged, and repaired across their lifetime. As age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area has neglected is how G-quadruplex (G4) DNA RNA (G4-DNA G4-RNA) mediate senescence. These non-canonical four-stranded structures most normative RNA-dependent processes, such as transcription, replication, translation, well pathogenic mechanisms, including genomic instability abnormal stress granule function. This review also highlights contribution G4s to sex differences in age-associated diseases emphasizes potential translational approaches target senescence anti-aging through G4 manipulation.

Language: Английский

Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging DOI Creative Commons
Wenchuan Zhang,

Chongtian Huang,

Haiyang Yao

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 25, 2025

Abstract Neurological disorders present considerable challenges in diagnosis and treatment due to their complex diverse etiology. Retrotransposons are a type of mobile genetic element that increasingly revealed play role these diseases. This review provides detailed overview recent developments the study retrotransposons neurodevelopment, neuroaging, neurological Retrotransposons, including long interspersed nuclear elements-1, Alu, SINE-VNTR-Alu, endogenous retrovirus, important regulatory roles development aging nervous system. They have also been implicated pathological processes several diseases, Alzheimer's disease, X-linked dystonia-parkinsonism, amyotrophic lateral sclerosis, autism spectrum disorder, schizophrenia. provide new perspective for understanding molecular mechanisms underlying diseases insights into diagnostic therapeutic strategies

Language: Английский

Citations

0
Review: Utility of mass spectrometry in rare disease research and diagnosis DOI Creative Commons
Teresa Zhao, Daniella H. Hock, James Pitt

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 31, 2025

Individuals affected by a rare disease often experience long and arduous diagnostic odyssey. Delivery of genetic answers in timely manner is critical to individuals their families. Multi-omics, term which usually encompasses genomics, transcriptomics, proteomics, metabolomics lipidomics, has gained increasing popularity research diagnosis over the past decade. Mass spectrometry (MS) technique allowing study proteins, metabolites lipids fragments at scale, enabling researchers effectively determine presence abundance thousands molecules single test, accurately quantify specific levels, identify potential therapeutic biomarkers, detect differentially expressed proteins patients with diseases, monitor progression treatment response. In this review, we focus on mass (MS)-based omics survey literature describing utility different MS-based how they have transformed diagnosis.

Language: Английский

Citations

0
SAK3 confers neuroprotection in the neurodegeneration model of X-linked Dystonia-Parkinsonism DOI
Shivani Aryal, Shawei Chen, Kyle F. Burbach

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 25, 2024

Abstract Background X-linked Dystonia-Parkinsonism(XDP) is an adult-onset neurodegenerative disorder that results in the loss of striatal medium spiny neurons (MSNs). XDP associated with disease-specific mutations and around TAF1 gene. This study highlights utility directly reprogrammed MSNs from fibroblasts affected individuals as a platform captures cellular epigenetic phenotypes XDP-related neurodegeneration. In addition, current demonstrates neuroprotective effect SAK3 currently tested other diseases. Methods three independent patients well age- sex-matched control were used to generate by direct neuronal reprogramming using miRNA-9/9*-124 thetranscription factors CTIP2, DLX1-P2A-DLX2, MYT1L. Neuronal death, DNA damage, mitochondrial health assays carried out assess state (XDP-MSNs). RNA sequencing ATAC performed infer changes transcriptomic chromatin landscapesof XDP-MSNs compared those (Ctrl-MSNs). Results Our show patient can be successfully into display several degenerative phenotypes, including dysfunction, Ctrl-MSNs individuals’ fibroblasts. showed increased vulnerability TNFα -toxicity Ctrl-MSNs. To dissect altered XDP-MSNs, we conducted accessibility analyses RNA- ATAC-seq. indicate pathways related function, calcium signaling, genes diseases are commonly multiple patients. Interestingly, found SAK3, T-type channel activator, may have therapeutic values disorders, protected death. Notably, SAK3-mediated alleviation neurodegeneration was accompanied gene expression toward

Language: Английский

Citations

0
Deciphering the Pathophysiological Mechanisms Underpinning Myoclonus Dystonia Using Pluripotent Stem Cell-Derived Cellular Models DOI Creative Commons
Zongze Li, Laura Abram, Kathryn J. Peall

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1520 - 1520

Published: Sept. 10, 2024

Dystonia is a movement disorder with an estimated prevalence of 1.2% and characterised by involuntary muscle contractions leading to abnormal postures pain. Only symptomatic treatments are available no disease-modifying or curative therapy, in large part due the limited understanding underlying pathophysiology. However, inherited monogenic forms dystonia provide opportunity for development disease models examine these mechanisms. Myoclonus Dystonia, caused

Language: Английский

Citations

0
G-quadruplex DNA and RNA in cellular senescence DOI Creative Commons

Rocio Diaz Escarcega,

Paul R. Marshall, Andrey S. Tsvetkov

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Oct. 9, 2024

Normal cells divide, are damaged, and repaired across their lifetime. As age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area has neglected is how G-quadruplex (G4) DNA RNA (G4-DNA G4-RNA) mediate senescence. These non-canonical four-stranded structures most normative RNA-dependent processes, such as transcription, replication, translation, well pathogenic mechanisms, including genomic instability abnormal stress granule function. This review also highlights contribution G4s to sex differences in age-associated diseases emphasizes potential translational approaches target senescence anti-aging through G4 manipulation.

Language: Английский

Citations

0