Single-cell sequencing uncovers the mechanistic role of DAPK1 in glioma and its diagnostic and prognostic implications

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 24, 2025

Background We conducted an investigation into the characteristics of single-cell differentiation data in gliomas, with a focus on developing DAPK1-based prognostic markers to predict patient outcomes. Dysregulated expression DAPK1 has been associated invasive behavior various malignancies, including gliomas. However, precise role and underlying mechanisms gliomas remain inadequately understood. Methods performed analyses RNA-seq microarray datasets from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO), addition RNA sequencing (scRNA-seq) glioma patients available GEO. Utilizing Seurat R package, we identified gene clusters survival scRNA-seq data. Prognostic models were developed using LASSO stepwise regression algorithms. Furthermore, assessed predictive potential these genes within immune microenvironment their relevance immunotherapy contexts. Results Our analysis revealed 32 distinct cell corresponding 10 types. Through dimensionality reduction clustering, three glial subpopulations based trajectories. DAPK1, serving as marker for terminal subpopulation, exhibited association poor prognosis. Conclusions show promise accurately predicting outcomes glioblastoma glioma. An in-depth examination DAPK1’s specific could elucidate its response. Targeting may offer therapeutic benefits patients.

Language: Английский

---

A dual “turn-on” biosensor based on AIE effect and FRET for in situ detection of miR-125b biomarker in early Alzheimer's disease

Biosensors and Bioelectronics, Journal Year: 2023, Volume and Issue: 230, P. 115270 - 115270

Published: March 31, 2023

Language: Английский

---

Regulation and mechanism of Astragalus polysaccharide on ameliorating aging in Drosophila melanogaster

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 234, P. 123632 - 123632

Published: Feb. 17, 2023

Language: Английский

---

The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities

Biomolecules, Journal Year: 2023, Volume and Issue: 13(3), P. 549 - 549

Published: March 17, 2023

Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects the elderly. One of key features AD accumulation reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) master regulator antioxidant response cells. Under low ROS levels, Nrf2 kept cytoplasm. However, production translocation into nucleus, where it activates transcription several genes involved cells’ response. Additionally, activation increases autophagy function. AD, Aβ and tau reduces decreasing reduced levels contribute further by impairing their autophagy-mediated turnover. In this review, we discuss overwhelming evidence indicating genetic or pharmacological as potential approach mitigate pathology.

Language: Английский

---

Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 9, 2024

Alzheimer's disease (AD) is the most prevalent form of dementia in elderly and represents a major clinical challenge ageing society. Neuropathological hallmarks AD include neurofibrillary tangles composed hyperphosphorylated tau, senile plaques derived from deposition amyloid-β (Aβ) peptides, brain atrophy induced by neuronal loss, synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) ubiquitously expressed central nervous system. Dysregulation DAPK1 has been shown to contribute various neurological diseases including AD, ischemic stroke Parkinson's (PD). We have established an upstream effect on Aβ tau pathologies apoptosis through kinase-mediated phosphorylation, supporting causal role pathophysiology AD. In this review, we summarize current knowledge about how involved pathological changes hyperphosphorylation, deposition, cell death degeneration. The underlying molecular mechanisms dysregulation are discussed. also review recent progress regarding development novel modulators their potential applications intervention. These findings substantiate as therapeutic target for multifunctional disease-modifying treatments other disorders.

Language: Английский

---

Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16259 - 16259

Published: Nov. 13, 2023

Alzheimer’s disease (AD) is a complex multifactorial disorder that poses substantial burden on patients, caregivers, and society. Considering the increased aging population life expectancy, incidence of AD will continue to rise in following decades. However, molecular pathogenesis remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, effective therapeutics halt or slow progression urgently needed. As powerful genetic regulators, microRNAs (miRNAs) receiving increasing attention due their implications initiation, development, theranostics various diseases, including AD. In this review, we summarize miRNAs directly target microtubule-associated protein tau (MAPT), amyloid precursor (APP), β-site APP-cleaving enzyme 1 (BACE1) transcripts regulate alternative splicing APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3β, cyclin-dependent 5 (CDK5), death-associated (DAPK1), well apolipoprotein E, targeted by control phosphorylation amyloidogenic APP processing leading Aβ pathologies. Moreover, there evidence miRNA-mediated modulation inflammation. Furthermore, circulating serum plasma patients noninvasive biomarkers with diagnostic potential reviewed. addition, miRNA-based optimized nanocarriers exosomes options treatment discussed.

Language: Английский

---

A new perspective on Alzheimer’s disease: microRNAs and circular RNAs

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 15, 2023

microRNAs (miRNAs) play a multifaceted role in the pathogenesis of Alzheimer’s disease (AD). miRNAs regulate several aspects disease, such as Aβ metabolism, tau phosphorylation, neuroinflammation, and synaptic function. The dynamic interaction between their target genes depends upon various factors, including subcellular localization miRNAs, relative abundance mRNAs, affinity miRNA-mRNA interactions. are released into extracellular fluids subsequently conveyed to specific cells through modes transportation, exosomes. In comparison, circular RNAs (circRNAs) non-coding RNA (ncRNA) characterized by covalently closed continuous loops. contrast linear RNA, molecules circularized forming covalent bonds 3′and 5′ends. CircRNA regulates gene expression with at either transcriptional or post-transcriptional level, even though precise functions mechanisms regulation remain be elucidated. current stage research on miRNA profiles for diagnostic purposes complex disorders is still its early phase, primarily due intricate nature underlying pathological causes, which encompass diverse range pathways targets. Hence, this review comprehensively addressed alteration across sources peripheral blood, exosome, cerebrospinal fluid, brain AD patients. This also addresses nascent involvement circRNAs prospective utility biomarkers therapeutic targets these conditions future research.

Language: Английский

---

Targeting Death-Associated Protein Kinases for Treatment of Human Diseases: Recent Advances and Future Directions

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(2), P. 1112 - 1136

Published: Jan. 16, 2023

The death-associated protein kinase (DAPK) family is a member of the calcium/calmodulin-regulated serine/threonine family, and studies have shown that its role, as name suggests, mainly to regulate cell death. DAPK comprises five members, including DAPK1, DAPK2, DAPK3, DRAK1 DRAK2, which show high homology in common N-terminal domain but differ extra-catalytic domain. Notably, previous research has suggested plays an essential role both development regulation human diseases. However, only few small-molecule inhibitors been reported. In this Perspective, we discuss structure, biological function, DAPKs diseases currently discovered inhibitors, providing valuable information for field.

Language: Английский

---

Role and Dysregulation of miRNA in Patients with Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 712 - 712

Published: Dec. 31, 2022

Parkinson's disease (PD) is a neurodegenerative synucleinopathy that has not yet fully understood molecular pathomechanism behind it. The role of risk genes regulated by small non-coding RNAs, or microRNAs (miRNAs), also been highlighted in PD, where they may influence progression and comorbidities. In this case-control study, we analyzed miRNAs on peripheral blood mononuclear cells means RNA-seq 30 participants, with the aim identifying differentially expressed PD compared to age-matched healthy controls. Additionally, investigated pathways influenced assessed whether specific pathway could potentially be associated susceptibility (enrichment analyses performed using Ingenuity Pathway Analysis tools). Overall, considering upregulation might related downregulation their messenger RNA targets, vice versa, found several putative targets dysregulated (i.e., upregulated: hsa-miR-1275, hsa-miR-23a-5p, hsa-miR-432-5p, hsa-miR-4433b-3p, hsa-miR-4443; downregulated: hsa-miR-142-5p, hsa-miR-143-3p, hsa-miR-374a-3p, hsa-miR-542-3p, hsa-miR-99a-5p). An inverse connection between cancer neurodegeneration, called "inverse comorbidity", noted, showing some oppositely disorders cancers. Therefore, it reasonable consider these as potential diagnostic markers outcome measures.

Language: Английский

---

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 44(1), P. 365 - 405

Published: Aug. 17, 2023

Diabetes and its complications, Alzheimer's disease (AD), Parkinson's (PD) are increasing gradually, reflecting a global threat vis-à-vis expressing the essentiality of substantial paradigm shift in research remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, half-life protein. Surprisingly, most proteins associated with metabolic neurodegenerative disorders generally long-lived hence susceptible to glycation. Remarkably, linked diabetes, AD, PD share this characteristic. This modulates protein's structure, aggregation tendency, toxicity, highlighting renovated attention. Gut microbes microbial metabolites marked their importance human health diseases. Though many scientific shreds evidence proposed for possible change dysbiosis gut flora these diseases, very little known about mechanisms. Screening unfolding functionality essential hunting treasure. Therefore, it imperative evaluate role as common link diabetes which helps clarify if modulation nonenzymatic may act beneficial therapeutic strategy microbes/metabolites answer some crucial questions. review briefly emphasizes functional attributes microbes, linkages, discusses current treatment options challenges.

Language: Английский

---