The Promise of Epigenetic Editing for Treating Brain Disorders

Sub-cellular biochemistry/Subcellular biochemistry, Год журнала: 2025, Номер unknown, С. 111 - 190

Опубликована: Янв. 1, 2025

Язык: Английский

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Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations

Cell & Bioscience, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 20, 2025

Abstract Background Cell-free DNA (cfDNA) in plasma carries epigenetic signatures specific to tissue or cell of origin. Aberrant methylation patterns circulating cfDNA have emerged as valuable tools for noninvasive cancer detection, prenatal diagnostics, and organ transplant assessment. Such changes also hold significant promise the diagnosis neurodegenerative diseases, which often progresses slowly has a lengthy asymptomatic period. However, genome-wide diseases remain poorly understood. Results We used whole-genome bisulfite sequencing (WGBS) profile age-dependent ALS-associated from 30 individuals, including young middle-aged controls, well ALS patients with matched controls. identified 5,223 age-related differentially methylated loci (DMLs) (FDR < 0.05), 51.6% showing hypomethylation older individuals. Our results significantly overlapped age-associated CpGs large blood-based epigenome-wide association study (EWAS). Comparing we detected 1,045 regions (DMRs) gene bodies, promoters, intergenic regions. Notably, these DMRs were linked key pathways, endocytosis adhesion. Integration spinal cord transcriptomics revealed that 31% DMR-associated genes exhibited differential expression compared over 20 correlating disease duration. Furthermore, comparison published single-nucleus RNA (snRNA-Seq) data demonstrated reflects cell-type-specific dysregulation brain patients, particularly excitatory neurons astrocytes. Deconvolution profiles suggested altered proportions immune liver-derived patients. Conclusions is powerful tool assessing ALS-specific molecular by revealing perturbed locus, genes, proportional contributions different tissues/cells plasma. This technique holds clinical application biomarker discovery across broad spectrum disorders.

Язык: Английский

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Exploring epigenetic modifications as potential biomarkers and therapeutic targets in amyotrophic lateral sclerosis

Journal of Neurology, Год журнала: 2025, Номер 272(4)

Опубликована: Апрель 1, 2025

Язык: Английский

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Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases

Biomolecules, Год журнала: 2024, Номер 14(11), С. 1366 - 1366

Опубликована: Окт. 27, 2024

Individuals affected by neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked onset diseases known, they can explain only a small portion cases. The etiopathology underlying process in most patients is likely due interplay between predisposing environmental factors. Epigenetic mechanisms, DNA methylation, central candidates translating effects factors genome modulation, play critical role etiology AD, PD, ALS. Among main exposures that have been an increased risk accumulating evidence points heavy metals, pesticides, air pollutants. These compounds could trigger neurodegeneration through different mainly neuroinflammation induction oxidative stress. However, suggests also capable inducing epigenetic alterations neurons. In this article, we review available literature linking exposure pollutants methylation changes relevant neurodegeneration.

Язык: Английский

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DNA methylation in amyotrophic lateral sclerosis: where do we stand and what is next?

Epigenomics, Год журнала: 2024, Номер unknown, С. 1 - 12

Опубликована: Сен. 11, 2024

Genes involved in immune response, inflammation and metabolism are among those most likely affected by changes DNA methylation (DNAm) expression levels amyotrophic lateral sclerosis (ALS) tissues. Unfortunately, it is still largely unclear whether any of these precede the onset disease symptoms or them result muscular metabolic that follow onset. In this article author discusses strengths limitations available studies DNAm ALS provides some suggestions on what, his opinion, could be done near future for a better understanding occurring ALS, their link with environmental exposures potential clinical utility.

Язык: Английский

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Clinical and genetic characteristics of ALS patients with variants in genes regulating DNA methylation

Journal of Neurology, Год журнала: 2024, Номер 271(8), С. 5556 - 5566

Опубликована: Июнь 22, 2024

Язык: Английский

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