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

Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies DOI Open Access
Aquene N. Reid, Suman Jayadev, Katherine E. Prater

et al.

Glia, Journal Year: 2025, Volume and Issue: 73(3), P. 519 - 538

Published: Jan. 6, 2025

Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes expressed in microglia-specific manner. However, while alterations microglial morphology and gene expression observed human postmortem brain tissue, mechanisms by which drive contribute AD pathology remain ill-defined. Numerous mouse models have been developed facilitate disambiguation biological underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, use multiple technologies including bulk tissue single cell transcriptomics, epigenomics, spatial proteomics, lipidomics, metabolomics shed light on heterogeneity phenotypes molecular patterns altered models. Each these 'omics provide unique information insight. Here, we review literature approaches findings methods synthesis knowledge generated applying AD.

Language: Английский

Citations

1
Alzheimer’s disease and infectious agents: a comprehensive review of pathogenic mechanisms and microRNA roles DOI Creative Commons

Seyyed Sam Mehdi Hosseininasab,

Rasoul Ebrahimi,

Shirin Yaghoobpoor

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 7, 2025

Alzheimer's Disease (AD) is the most prevalent type of dementia and characterized by presence senile plaques neurofibrillary tangles. There are various theories concerning causes AD, but connection between viral bacterial infections their potential role in pathogenesis AD has become a fascinating area research for field. Various viruses such as Herpes simplex virus 1 (HSV-1), Epstein-Barr (EBV), Cytomegalovirus (CMV), influenza viruses, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), well bacteria Chlamydia pneumoniae (CP), Helicobacter pylori (HP), Porphyromonas gingivalis (P. gingivalis), Spirochetes eukaryotic unicellular parasites (e.g., Toxoplasma gondii), have been linked to due ability activate immune system, induce inflammation increase oxidative stress, thereby leading cognitive decline AD. In addition, microRNAs (miRNAs) might play crucial mechanisms these pathogens since they utilized target protein-coding genes, allowing evasion, maintaining latency, suppressing cellular signaling molecules. Also, can regulate gene expression human cells. This article provides an overview association infectious agents, with focus on which may be related These findings suggest important areas further explored future studies.

Language: Английский

Citations

1
Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics DOI Creative Commons
Daniela Dias, Renato Socodato

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 279 - 279

Published: Jan. 23, 2025

Alzheimer’s disease (AD) is traditionally viewed through the lens of amyloid cascade hypothesis, implicating amyloid-beta and tau protein aggregates as main pathological culprits. However, burgeoning research points to brain’s resident immune cells, microglia, critical players in AD pathogenesis, progression, potential therapeutic interventions. This review examines dynamic roles microglia within intricate framework AD. We detail involvement these cells neuroinflammation, explaining how their activation response fluctuations may influence trajectory. further elucidate complex relationship between pathology. study highlights dual nature which contribute both aggregation clearance protein. Moreover, an in-depth analysis interplay unveils significant, yet often overlooked, impact this interaction on neurodegeneration Shifting from conventional approaches, we assess current treatments primarily targeting introduce novel strategies that involve manipulating microglial functions. These innovative methods herald a paradigm shift management Finally, explore field precision diagnosis pursuit robust biomarkers. underline more profound comprehension biology could enrich essential areas, potentially paving way for accurate diagnostic tools tailored treatment strategies. In conclusion, expands perspective pathology treatment, drawing attention multifaceted microglia. As continue enhance our understanding microglial-focused interventions emerge promising frontier bolster arsenal fight against

Language: Английский

Citations

1
Blood-Based Biomarkers in Alzheimer’s Disease: Advancing Non-Invasive Diagnostics and Prognostics DOI Open Access
Mrinmay Dhauria, Ritwick Mondal, Shramana Deb

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 10911 - 10911

Published: Oct. 10, 2024

Alzheimer’s disease (AD), the most prevalent form of dementia, is expected to rise dramatically in incidence due global population aging. Traditional diagnostic approaches, such as cerebrospinal fluid analysis and positron emission tomography, are expensive invasive, limiting their routine clinical use. Recent advances blood-based biomarkers, including amyloid-beta, phosphorylated tau, neurofilament light, offer promising non-invasive alternatives for early AD detection monitoring. This review synthesizes current research on these highlighting potential track pathology enhance accuracy. Furthermore, this uniquely integrates recent findings protein-protein interaction networks microRNA pathways, exploring novel combinations proteomic, genomic, epigenomic biomarkers that provide new insights into AD’s molecular mechanisms. Additionally, we discuss integration with advanced neuroimaging techniques, emphasizing revolutionize diagnostics. Although large-scale validation still needed, represent a critical advancement toward more accessible, cost-effective, tools AD.

Language: Английский

Citations

4
How Histone Sensing Drives Alzheimer’s Disease DOI Creative Commons
Jia‐Ping Wu

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 18, 2025

The human DNA double helix is wrapped around proteins known as histones, which play a critical role in regulating gene expression. goal of this opinion piece to provide an overview how histone sensing drives Alzheimer’s disease (AD). Histones are enriched basic amino acids. Histone acetylation plays important the progression AD its dysregulation can lead neuroinflammation and neurodegenerative diseases. Specifically, abnormal acetylation, post-translation modification, key factor it contributes brain cell inflammatory pathology. Thus, higher levels could potentially serve biomarkers for AD. Here, we report that increased histones H2B, H3, H4 promoter regions Tip60 lysine acetyltransferase protein, p300/CREB-binding protein (CBP), GCN5-related N-acetyltransferases, p300/CBP-associated factor, elongator 3, brain-derived neurotrophic Tau genes hippocampus temporal lobe associated with development AD-associated learning memory impairment.

Language: Английский

Citations

0
Revealing Lingonberry’s Neuroprotective Potential in Alzheimer’s Disease Through Network Pharmacology and Molecular Docking DOI Open Access

J Li,

Mian Wang, Yi Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2363 - 2363

Published: March 6, 2025

Alzheimer's disease is a progressive neurodegenerative disorder with limited treatment options. Lingonberry (Vaccinium vitis-idaea L.) has demonstrated neuroprotective and anti-inflammatory properties, yet the underlying mechanisms remain unclear. This study employed network pharmacology, molecular docking, dynamics simulations to explore therapeutic potential in disease. Pathway analysis identified monoamine oxidase B as key target involved serotonergic synapse dysfunction related Molecular docking revealed that ferulic acid, major bioactive compound lingonberry, exhibits strong binding affinity B. Further confirmed stability of this interaction, highlighting inhibitory effect acid on These findings provide novel insights into lingonberry suggest its natural intervention for

Language: Английский

Citations

0
Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease DOI Creative Commons

Tingting Ruan,

Yunxiang Ling,

Can Wu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

Citations

0
Evaluation of Illumina and Oxford Nanopore Sequencing for the Study of DNA Methylation in Alzheimer’s Disease and Frontotemporal Dementia DOI Open Access
Lorenzo Pagano, Davide Lagrotteria, Alessandro Facconi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4198 - 4198

Published: April 28, 2025

DNA methylation is a critical epigenetic mechanism involved in numerous physiological processes. Alterations patterns are associated with various brain disorders, including dementias such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Investigating these alterations essential for understanding the pathogenesis progression of disorders. Among methods detecting methylation, sequencing one most widely employed. Specifically, two main approaches commonly used analysis: bisulfite single-molecule long-read sequencing. In this review, we compared performances CpG detection obtained using popular platforms, Illumina Oxford Nanopore (ON) Our comparison considers several factors, accuracy, efficiency, genomic regions, costs, wet-lab protocols, bioinformatics pipelines. We provide insights into strengths limitations both particular focus on their application research AD FTD.

Language: Английский

Citations

0
Identifying the mediating role of brain atrophy on the relationship between DNA damage repair pathway and Alzheimer's disease: A Mendelian randomization analysis and mediation analysis DOI

Wei Bao,

Haidi Bi,

Lishuo Chao

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Background DNA damage and repair (DDR) structural atrophies in different brain regions were recognized as critical factors the onset of Alzheimer's disease (AD). Objective We utilized Mendelian randomization (MR) to examine causal effects DDR-related molecular traits on AD potential mediating roles region volumes. Methods In primary analysis, we public genome-wide association studies summary data from existing datasets, including gene expression, methylation, protein levels quantitative trait loci (eQTL, mQTL, pQTL) both blood their associations by summary-data-based MR analysis additional five two-sample methods. Subsequently, mediation explored mediate 13 imaging-derived volume phenotypes between DDR pathways through a network design. Results found that volumes right thalamus proper global cerebral white matter mediated EGFR relatively weak lateral ventricle involving CHRNE, DNTT, AD. Conclusions identified relationships among pathways, specific volumes, Monitoring these genes developing targeted drugs may help detect interrupt early progression

Language: Английский

Citations

0
Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement DOI Open Access
Cristina Popescu, Constantin Munteanu, Aurelian Anghelescu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11272 - 11272

Published: Oct. 19, 2024

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through microbiota–gut–brain axis, including Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis recent findings on involvement neuroinflammatory processes associated with AD, emphasizing novel insights therapeutic implications. reveals that dysbiosis AD patients’ is linked heightened peripheral central inflammatory responses. Specific bacterial taxa, such as Bacteroides Firmicutes gut, well Porphyromonas gingivalis cavity, are notably altered leading significant changes microglial activation cytokine production. Gut alterations increased intestinal permeability, facilitating translocation endotoxins like lipopolysaccharides (LPS) into bloodstream exacerbating by activating brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, short-chain fatty acids (SCFAs) amyloid peptides, can cross blood-brain barrier modulate While microbial amyloids may contribute amyloid-beta aggregation brain, certain SCFAs butyrate exhibit anti-inflammatory properties, suggesting potential avenue mitigate neuroinflammation. not only highlights critical pathology but also offers ray hope modulating could represent strategy for reducing slowing progression.

Language: Английский

Citations

3