Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)
Published: Aug. 28, 2024
Language: Английский
Citations
23
Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208
Published: Oct. 8, 2024
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.
Language: Английский
Citations
10
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
Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 168 - 168
Published: Jan. 22, 2025
The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression
Language: Английский
Citations
1
Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00540 - e00540
Published: Feb. 1, 2025
Astrocytes and oligodendrocytes, once considered passive support cells, are now recognized as active participants in the pathogenesis of Alzheimer's disease. Emerging evidence highlights critical role that these glial cells play pathological features Alzheimer's, including neuroinflammation, excitotoxicity, synaptic dysfunction, myelin degeneration, which contribute to neurodegeneration cognitive decline. Here, we review current understanding astrocyte oligodendrocyte pathology disease highlight research supports therapeutic potential modulating functions treat
Language: Английский
Citations
1
Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1737 - 1737
Published: Aug. 2, 2024
Microglial cells exhibit properties akin to macrophages, thereby enabling them support and protect the central nervous system environment. Aging induces alterations in microglial polarization, resulting a shift toward neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation cells' regulatory pathways interactions with neurons contribute chronic activation neurodegeneration. A better understanding involvement microglia neurodegenerative diseases such as Alzheimer's Parkinson's is critical topic for studying role inflammatory responses disease progression. Furthermore, metabolic changes aged microglia, including downregulation oxidative phosphorylation, are discussed this review. Understanding these mechanisms crucial developing preventive therapeutic strategies.
Language: Английский
Citations
5
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9475 - 9475
Published: Aug. 31, 2024
Alzheimer's disease (AD), the leading cause of dementia, is a multifactorial influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators gene expression play significant roles in AD onset progression. This exploratory study analyzed levels 28 genes 5 (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, miR-155-5p) related to pathology neuroimmune responses using RT-qPCR. Analyses were conducted prefrontal cortex (PFC) hippocampus (HPC)
Language: Английский
Citations
4
Neurotherapeutics, Journal Year: 2025, Volume and Issue: 22(3), P. e00519 - e00519
Published: Jan. 6, 2025
Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including toxic secretome and resistance to apoptosis. When form faster than they are cleared the immune system, accumulate in tissues throughout body contribute age-related diseases, neurodegeneration. This review highlights evidence of brain their role Alzheimer's disease (AD), leading cause dementia older adults. We also discuss progress challenges senotherapies, pharmacological strategies clear mitigate effects, which hold promise as interventions for AD related dementias (ADRD).
Language: Английский
Citations
0
Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 14, 2025
Abstract INTRODUCTION Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics‐driven research has revealed associations between vascular abnormalities transcriptomic alterations brain cells, particularly endothelial cells (ECs) pericytes (PCs). However, impact these molecular changes on remains unclear. METHODS We conducted comparative analysis gene expression ECs PCs across conditions, including Alzheimer's disease (AD), Huntington's disease, arteriovenous malformation, utilizing data from published postmortem human tissue studies. RESULTS identified differentially expressed genes (DEGs) consistently dysregulated pathologies. Notably, several DEGs are linked to cell zonation genetic risks for AD cerebral small vessel disease. DISCUSSION Our findings provide insights into cellular mechanisms underlying dementia, highlight knowledge gaps, suggest potential novel therapeutic targets, not previously investigated this context. Highlights Systematic review single‐nuclear RNA‐sequencing (snRNA‐seq) Identify overlapping multiple types Examine functional relevance with risk common DEGs. Outline future directions omics field.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 25, 2025
Alzheimer's disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple types. Here, we first performed a meta-analysis single-nucleus transcriptomic (snRNAseq) data from 869 brains diverse decedents, confirming critical role an SLC38A2 high SMTN CACNA1D astrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated signaling drivers Ast10's aging brain, focusing on interactions among microglial astrocytic subsets. Analysis snRNAseq prioritized set ligands receptors that are robustly predictive Ast10 proportions participants, confirm our predictions studies. Independent validation with spatial transcriptomics reveals striking colocalization these signature brain tissue, but not other states. Genetic ablation top receptor PLXNB1 murine human iPSC-derived astrocytes decreased signature, its regulatory role. Finally, find may contribute to decline through synaptic loss associated independent AD. Thus, regulators potential points convergence for neurodegenerative mechanisms be promising targets therapeutic development preserve function.
Language: Английский
Citations
0