Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome DOI Open Access
Alejandro Borrego-Ruiz, Juan J. Borrego

Genes, Journal Year: 2024, Volume and Issue: 15(12), P. 1599 - 1599

Published: Dec. 14, 2024

Background/Objectives: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result transcriptional changes, which play significant role onset of age-related diseases, including cancer, cardiovascular disease, diabetes, neurodegenerative disorders. For this reason, epigenetic diseases have been reviewed, major extrinsic factors influencing these identified. In addition, gut microbiome its metabolites as modifiers has addressed. Results: Long-term exposure to such air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, stress provoke changes host through several endocrine immune pathways, potentially accelerating process. Diverse studies reported plays critical regulating brain cell functions DNA methylation histone modifications. The interaction between genes serves source adaptive variation, contributing phenotypic plasticity. However, molecular mechanisms signaling pathways driving are still not fully understood. Conclusions: Extrinsic potential inducers alterations, may important implications for longevity. an effector gene expression modifications, while bidirectional interactions with underexplored roles non-bacterial microorganisms fungi viruses highlight need further research.

Language: Английский

RNA modifications in physiology and disease: towards clinical applications DOI Open Access
Sylvain Delaunay, Mark Helm, Michaela Frye

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 104 - 122

Published: Sept. 15, 2023

Language: Английский

Citations

121
Precision RNA base editing with engineered and endogenous effectors DOI
Laura S. Pfeiffer, Thorsten Stafforst

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(11), P. 1526 - 1542

Published: Sept. 21, 2023

Language: Английский

Citations

31
Disrupting pathologic phase transitions in neurodegeneration DOI Creative Commons

Bryan Hurtle,

Longxin Xie, Christopher J. Donnelly

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(13)

Published: July 2, 2023

Solid-like protein deposits found in aged and diseased human brains have revealed a relationship between insoluble accumulations the resulting deficits neurologic function. Clinically diverse neurodegenerative diseases, including Alzheimer's disease, Parkinson's frontotemporal lobar degeneration, amyotrophic lateral sclerosis, exhibit unique disease-specific biochemical signatures abnormal depositions that often correlate with disease pathogenesis. Recent evidence indicates many pathologic proteins assemble into liquid-like phases through highly coordinated process of liquid-liquid phase separation. Over last decade, biomolecular transitions emerged as fundamental mechanism cellular organization. Liquid-like condensates organize functionally related biomolecules within cell, neuropathology-associated reside these dynamic structures. Thus, examining enhances our understanding molecular mechanisms mediating toxicity across diseases. This Review explores known contributing to aberrant focusing on tau TDP-43 proteinopathies outlining potential therapeutic strategies regulate events.

Language: Английский

Citations

22
Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment DOI Creative Commons

Liriopé Toupenet Marchesi,

Daniel Stockholm, Typhaine Esteves

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 18, 2025

Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, type 11 (SPG11) represents complex form HSP caused by deleterious variants in the SPG11 gene, which encodes spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement lysosome and autophagy mechanisms, neuronal neurites development or mitochondria function. Despite these findings, precise function protein remains elusive. To elucidate function, we conducted an extensive RNA sequencing (RNAseq) experiment transcriptomic analysis three distinct neural structures (cerebellum, cortex hippocampus) at different ages (6 weeks, 4 months 8 months) both wild Spg11−/− mice. Our functional differentially expressed genes (DEGs) Gene Set Enrichment Analysis (GSEA) revealed dysregulation pathways related to inflammation, metabolism neurite development, factors frequently implicated neurodegenerative disorders. Notably, also observed early deregulation cellular cell proliferation. results represent significant step towards better understanding functions underlying mechanisms disrupted absence.

Language: Английский

Citations

1
Regulation and roles of RNA modifications in aging‐related diseases DOI
Zeyidan Jiapaer, Dingwen Su, Lingyang Hua

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 21(7)

Published: June 19, 2022

With the aging of global population, accumulating interest is focused on manipulating fundamental aging-related signaling pathways to delay physiological process and eventually slow or prevent appearance severity multiple diseases. Recently, emerging evidence has shown that RNA modifications, which were historically considered infrastructural features cellular RNAs, are dynamically regulated across most species in cells thereby critically involved major biological processes, including senescence aging. In this review, we summarize current knowledge about modifications provide a catalog different species, mRNAs, miRNAs, lncRNA, tRNAs, rRNAs. Most importantly, focus regulation roles these diseases, neurodegenerative cardiovascular cataracts, osteoporosis, fertility decline. This would be an important step toward better understanding mechanisms facilitating development novel diagnostics therapeutics for

Language: Английский

Citations

34
A dual-excitation-driven full-component-responsive lanthanide-based metal-organic framework for switchable profiling of multi-disease markers DOI
Guoli Chen, Bin Dai, Ji‐Na Hao

et al.

Science China Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

Citations

0
Neuroepigenetics of ageing and neurodegeneration-associated dementia: An updated review DOI
Fayaz Ahmad Mir, Ayeman Amanullah, Buddhi Prakash Jain

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102067 - 102067

Published: Sept. 9, 2023

Language: Английский

Citations

11
Synthesis of RNA conjugates as bisubstrates for the study of transferases DOI Creative Commons
Laura Iannazzo, Emmanuelle Braud, Matthieu Fonvielle

et al.

Comptes Rendus Chimie, Journal Year: 2025, Volume and Issue: 28(G1), P. 111 - 129

Published: Feb. 13, 2025

Bisubstrate compounds are designed to mimic the interaction of enzymes with their two natural substrates. These molecules contain moieties mimicking substrates linked together by a covalent bridge, which enhances both selectivity and potency. This review shows synthesis utility RNA conjugates, particularly peptidyl–RNA cofactor–RNA as bisubstrate analogues for studying major families transferases: Fem aminoacyl transferases involved in bacterial cell wall m6A methyltransferases, catalyze methylation. The synthetic routes developed access conjugates cover nucleoside nucleotide chemistry, site-specific modifications, solid phase or chemoenzymatic processes well strategies oligonucleotide late-stage functionalization. have been used not only inhibitors these but also valuable chemical tools elucidating enzyme mechanisms facilitating structural studies. Les composés bisubstrats sont conçus pour imiter l'interaction entre les et leurs deux substrats naturels. Ces molécules contiennent fragments qui miment de l'enzyme, liés eux par un lien covalent, ce permet d'améliorer à la fois sélectivité puissance des composés. Cette revue présente synthèse l'utilisation conjugués d'ARN, en particulier peptidyl-ARN cofacteur-ARN, comme étudier grandes familles d'ARN transférases : aminoacyl-transférases impliquées dans paroi cellulaire bactérienne méthyltransférases catalysent méthylation l'ARN. voies développées accéder aux font appel chimie nucléosides nucléotides, réactions chimio spécifiques, sur support solide, processus chimio-enzymatiques, ou stratégies fonctionnalisation tardive oligonucléotides. ont été utilisées inhibiteurs transférases, mais également outils chimiques faciliter études structurales élucider mécanismes enzymatiques.

Citations

0
Pharmacology of Epitranscriptomic Modifications: Decoding the Therapeutic Potential of RNA Modifications in Drug Resistance DOI
Abdullah Alkhammash

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 994, P. 177397 - 177397

Published: Feb. 18, 2025

Language: Английский

Citations

0
RNA‐Based Therapies for Neurodegenerative Diseases Targeting Pathogenic Proteins DOI
Syed Arman Rabbani, Mohamed El‐Tanani, Shrestha Sharma

et al.

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(8)

Published: April 1, 2025

ABSTRACT Neurodegeneration is featured by the gradual stagnation of neuronal function and structure, leading to significant motor cognitive impairments. The primary histopathological features underlying these conditions include cumulation pathological protein aggregates, chronic inflammation, cell death. Alzheimer's disease ( AD ) Parkinson's (PD) are prominent examples neurodegenerative diseases (NDDs). As 2023, over 65 million people worldwide affected PD, with prevalence steadily increasing time. Interestingly, there no effective therapies available halt or slow NDD progression. Most approved treatments focused on symptom management often associated substantial side effects. Given limitations, development novel therapeutic approaches targeting molecular mechanisms disorders essential. Notably, RNA‐based therapeutics have recently emerged as a potential approach for managing various neurological diseases, offering innovative interventions in NDD. In this review, we discussed pathogenic role aggregates highlighted emerging strategies aimed at proteins.

Language: Английский

Citations

0