Integrating epigenetic modification and stem cell therapy strategies: A novel approach for advancing Alzheimer's disease treatment - A literature review. DOI
Edhijanto Widaja, Jeanne Adiwinata Pawitan

PubMed, Journal Year: 2024, Volume and Issue: 4(3), P. e935 - e935

Published: Dec. 1, 2024

Alzheimer's disease (AD) is the most frequent form of dementia and represents an increasing global burden, particularly in countries like Indonesia, where population has begun to age significantly. Current medications, including cholinesterase inhibitors NMDA receptor antagonists, have modest effects on clinical symptoms early middle stages, but there no curative treatment available so far despite progress. Activating or repressing epigenetic modifications, DNA methylation, histone modification microRNA regulation, appears play important role AD development. These alterations further enact transcriptional changes relevant signature pathologies amyloid-β deposition, tau protein malfunctioning, neuroinflammation, neuronal death. Here, we discuss feasibility targeting these as a new strategy due reversibility epigenetics their ability correct faulty gene expression. We also review combined promise stem cell therapies modulation neurodegeneration, inflammation cognitive decline. This approach may provide multifaceted slow progression, replace lost neurons, restore neural function. Despite challenges, ethical, financial, methodological barriers, ongoing research therapy holds for pioneering AD.

Language: Английский

Research on Prediction of Multiple Degenerative Diseases and Biomarker Screening Based on DNA Methylation DOI Open Access
Run Tian, Hao Zhang, Chencai Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 313 - 313

Published: Jan. 1, 2025

The aging process will lead to a gradual functional decline in the human body, and even accelerate significantly increased risk of degenerative diseases. DNA methylation patterns change markedly with one’s age, serving as biomarker biological age closely linked occurrence progression age-related Currently, diagnostic methods for individual diseases are relatively mature. However, often accompanies onset multiple diseases, presenting certain limitations existing models. Additionally, some identified biomarkers typically applicable only one or few types cancer further restricting their utility. We endeavor screen associated from perspective aging-related co-morbid mechanisms perform disease diagnoses. In this study, we explored research based on correlations investigate shared across identifying set them. validated these omics analysis prediction classes screened 600 110 by analysis, demonstrated validity predictive ability biomarkers. propose model multi-scale one-dimensional convolutional neural network (MSDCNN) multi-class (ResDegNet). two models well trained tested accurately diagnose categorize four providing foundation exploration conditions. This work aims facilitate early diagnosis, identification biomarkers, development therapeutic targets drug interventions.

Language: Английский

Citations

1
Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases DOI Open Access
Zheng Liu, Siyuan Song

Genes, Journal Year: 2025, Volume and Issue: 16(2), P. 135 - 135

Published: Jan. 24, 2025

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and amyotrophic lateral sclerosis (ALS), represent a growing societal challenge due to their irreversible progression significant impact on patients, caregivers, healthcare systems. Despite advances in clinical imaging-based diagnostics, these diseases are often detected at advanced stages, limiting the effectiveness of therapeutic interventions. Recent breakthroughs genomic transcriptomic technologies, including whole-genome sequencing, single-cell RNA sequencing (scRNA-seq), CRISPR-based screens, have revolutionized field, offering new avenues for early diagnosis personalized prognosis. Genomic approaches elucidated disease-specific genetic risk factors molecular pathways, while studies identified stage-specific biomarkers that correlate with severity. Furthermore, genome-wide association (GWAS), polygenic scores (PRS), spatial transcriptomics enabling stratification patients based profiles prognostic trajectories. Advances functional genomics uncovered actionable targets, ATXN2 ALS TREM2 AD, paving way tailored strategies. achievements, challenges remain translating discoveries into practice heterogeneity complexity neurodegenerative pathophysiology. Future integration technologies holds promise transforming diagnostic paradigms, hope improved patient outcomes precision medicine approaches.

Language: Английский

Citations

1
Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets DOI Creative Commons
Swagata Ghatak, Jolene K. Diedrich,

Maria Talantova

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(29)

Published: May 21, 2024

Abstract Standard single‐cell (sc) proteomics of disease states inferred from multicellular organs or organoids cannot currently be related to physiology. Here, a scPatch‐Clamp/Proteomics platform is developed on single neurons generated hiPSCs bearing an Alzheimer's (AD) genetic mutation and compares them isogenic wild‐type controls. This approach provides both current voltage electrophysiological data plus detailed information single‐cells. With this new method, the authors are able observe hyperelectrical activity in AD hiPSC‐neurons, similar that observed human brain, correlate it ≈1400 proteins detected at neuron level. Using linear regression mediation analyses explore relationship between abundance individual neuron's mutational status, yields therapeutic targets excitatory not attainable by traditional methods. combined patch‐proteomics technique creates proteogenetic‐therapeutic strategy genotypic alterations physiology with protein expression

Language: Английский

Citations

7
Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women DOI Creative Commons
Aziz Elbasheir, Şeyma Katrinli, Breanne E. Kearney

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(6), P. e2416588 - e2416588

Published: June 13, 2024

Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement deep regions (brainstem and midbrain) these responses is unknown. Potential associations racial with alterations functional connectivity accelerated epigenetic aging, a process that substantially vulnerability to problems, are also

Language: Английский

Citations

7
Epigenetics in Alzheimer’s Disease: A Critical Overview DOI Open Access
Chiara Villa, Romina Combi

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5970 - 5970

Published: May 29, 2024

Epigenetic modifications have been implicated in a number of complex diseases as well being hallmark organismal aging. Several reports indicated an involvement these changes Alzheimer’s disease (AD) risk and progression, most likely contributing to the dysregulation AD-related gene expression measured by DNA methylation studies. Given that is tissue-specific AD brain disorder, limitation studies ability identify clinically useful biomarkers proxy tissue, reflective tissue interest, would be less invasive, more cost-effective, easily obtainable. The age-related also used develop different generations epigenetic clocks devoted measuring aging tissues sometimes suggests age acceleration patients. This review critically discusses measures potential for detection, prognosis, progression. alterations are chemically reversible, treatments aiming at reversing will discussed promising therapeutic strategies AD.

Language: Английский

Citations

5
Magnesium and Longevity DOI Creative Commons
Patrick Chambers

Published: Nov. 7, 2024

Magnesium (Mg) is not prominent among the list of well known anti-aging agents. Yet signs and symptoms aging mimic those Mg deficiency. required for over 800 enzymatic reactions (as 2022). This review does correlate status with clinical data on agents linked to longevity. The approach physiologic highlights specific dependent by these longevity biomarkers. Many share common pathways extend healthspan. a cofactor in synthesis vitamin D melatonin activation six eight B vitamins. It all CYP450 enzymes. directly responsible appropriate methylation proteins DNA, which control epigenome. MTHFR (methylenetetrahydrofolate reductase) 677T allele that compromises present majority Americans. Aberrant predicts severity Covid-19 its persistence into long Covid. silent benefactor may indirectly link agents, but only if viewed context calcium (Ca), i.e., Ca:Mg. Both compete same receptor. To fully exploit sufficient required. pertinent physiology presented.

Language: Английский

Citations

5
EpiAge: a next-generation sequencing-based ELOVL2 epigenetic clock for biological age assessment in saliva and blood across health and disease DOI Creative Commons
David Cheishvili, Sonia Do Carmo, Filippo Caraci

et al.

Aging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

This study introduces EpiAgePublic, a new method to estimate biological age using only three specific sites on the gene ELOVL2, known for its connection aging. Unlike traditional methods that require complex and extensive data, our model uses simpler approach is well-suited next-generation sequencing technology, which more advanced of analyzing DNA methylation. overcomes some common challenges found in older methods, such as errors due sample quality processing variations. We tested EpiAgePublic with large varied group over 4,600 people ensure accuracy. It performed par with, sometimes better than, complicated models use much data estimation. examined effectiveness understanding how factors like HIV infection stress affect aging, confirming usefulness real-world clinical settings. Our results prove simple yet effective model, can capture subtle signs aging high also used this involving patients Alzheimer's Disease, demonstrating practical benefits making precise age-related assessments. lays groundwork future research mechanisms assessing different interventions might impact process clock.

Language: Английский

Citations

0
IDENTIFICATION OF EPIGENETIC CHANGE PATTERNS IN NEURODEGENERATIVE DISEASES (literature review) DOI Creative Commons

I. M. Trofimova,

V. V. Mikhajlovska,

С. В. Зябліцев

et al.

Medical Science of Ukraine (MSU), Journal Year: 2025, Volume and Issue: 21(1), P. 140 - 148

Published: March 31, 2025

Backround. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's and Huntington's are among the leading causes of disability in elderly. These conditions pose a significant socio-economic burden necessitate novel approaches to diagnosis therapy due their complex pathogenesis lack effective treatments. Epigenetic changes, particularly DNA methylation, histone modifications, microRNA regulation, play pivotal role development these diseases. Aim: conduct literature review aimed at identifying key epigenetic changes associated with neurodegenerative diseases therapeutic prospects. Materials methods. Specialized scientific from four databases—PubMed, Web Science, Scopus, Google Scholar—was analyzed. Search terms included "neurodegenerative diseases," "Alzheimer's disease," "Parkinson's "Huntington's "epigenetics," "HDAC inhibitors," "CRISPR/Cas9." The selected was limited English-language publications, analytical reviews, original research articles, an emphasis on recent works published over past 20 years. Results. outlines specific patterns changes. Promising strategies, deacetylase (HDAC) inhibitors CRISPR/Cas9 gene-editing technology, demonstrate potential for correcting abnormalities. Conclusion. analysis studies confirms that changes—specifically methylation patterns, dysregulation non-coding RNAs—hold promise early Further should focus refining developing strategies.

Language: Английский

Citations

0
Identification of diagnostic DNA methylation markers in the blood of Japanese Alzheimer’s disease patients using methylation capture sequencing DOI
Risa Mitsumori,

Kazuhide Sawamura,

Kimi Yamakoshi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Abstract Background Methylation capture sequencing (MC-seq), which relies on next-generation technology, offers advantages over the widely used array-based approach that Illumina Inc. developed regarding both resolution and comprehensiveness for detecting DNA methylation changes across genomes. In present study, MC-seq was employed first time to identify markers Alzheimer’s disease (AD). Results We compared in blood of 12 AD patients with brain amyloidosis cognitively normal elderly Japanese individuals without amyloidosis. Candidate differences were validated two cohorts using bisulfite amplicon sequencing. Significant differentially methylated regions identified ANKH, MARS, ANKFY1, LINC00908, KLF2 genes a slight change CHRNE (p = 0.061). Furthermore, our diagnostic prediction model showed combining levels ANKH MARS APOE genotype provided accuracy, achieving AUCs 0.90 0.81 discovery validation datasets, respectively. Conclusions The results suggest potential these diagnosing support validity identifying disease-related

Language: Английский

Citations

0
Differential methylation region detection via an array-adaptive normalized kernel-weighted model DOI Creative Commons
Daniel Alhassan, Gayla R. Olbricht, Akim Adekpedjou

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(6), P. e0306036 - e0306036

Published: June 28, 2024

A differentially methylated region (DMR) is a genomic that has significantly different methylation patterns between biological conditions. Identifying DMRs conditions critical for developing disease biomarkers. Although methods detecting in microarray data have been introduced, with high precision, recall, and accuracy determining the true length of remains challenge. In this study, we propose normalized kernel-weighted model to account similar profiles using relative probe distance from "nearby" CpG sites. We also extend by proposing an array-adaptive version attempt differences spacing Illumina's Infinium 450K EPIC bead array respectively. study asymptotic results our proposed statistic. compare approach popular DMR detection method via simulation studies under large small treatment effect settings. discuss susceptibility these two Lastly, demonstrate usefulness when combined pathway analysis on oral cancer data. created R package called idDMR, downloadable GitHub repository link: https://github.com/DanielAlhassan/idDMR, allows convenient implementation method.

Language: Английский

Citations

2