The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

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

---

A microglia-containing cerebral organoid model to study early life immune challenges

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

---

Microglia – Role in Immunity

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

---

The Ambiguous Role of Growth Factors in Autism: What Do We Really Know?

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1607 - 1607

Published: Feb. 13, 2025

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial origins, including the potential involvement of neurotrophins and growth factors. These molecules, which are crucial for neuronal survival, synaptic plasticity, brain development, have been implicated in ASD pathophysiology. Altered levels such as NGF, BDNF, NT3, NT4, well factors like IGF1, VEGF, FGF, associated cognitive deficits, sensory processing abnormalities, behavioral issues patients. However, literature presents conflicting results, often due to differences research methodologies, sample sizes, patient populations, diagnostic criteria. Despite these inconsistencies, biomarkers therapeutic targets remains promising. Future standardized larger cohorts, clearer understanding genetic influences needed further elucidate their roles diagnosis treatment.

Language: Английский

---

The Complementary Role of Morphology in Understanding Microglial Functional Heterogeneity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3811 - 3811

Published: April 17, 2025

A search of the PubMed database for publications on microglia reveals an intriguing shift in scientific interest over time. Dividing into categories such as “resting” and “activated” or M1 versus M2 is nowadays obsolete, with current research focusing unraveling microglial heterogeneity. The onset transcriptomics, especially single-cell RNA sequencing (scRNA-seq), has profoundly reshaped our understanding Conversely, morphology analysis can offer important insights regarding their activation state involvement tissue responses. This review explores heterogeneity under homeostatic conditions, developmental stages, disease states, a focus integrating transcriptomic data morphological analysis. Beyond core gene expression profile, regional differences are observed cerebellar exhibiting uniquely immune-vigilant profile. During development, express genes before birth, yet bushy appearance characteristic that appears later on. In neurodegeneration, alternate between proinflammatory neuroprotective roles, influenced by factors onset. Understanding these structural adaptations may help identify specific subpopulations targeted therapeutic strategies.

Language: Английский

---

M2 microglia-derived small extracellular vesicles modulate NSC fate after ischemic stroke via miR-25-3p/miR-93-5p-TGFBR/PTEN/FOXO3 axis

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 23, 2025

Endogenous neurogenesis could promote stroke recovery. Furthermore, anti-inflammatory phenotypical microglia (M2-microglia) facilitate Neural Stem Cell (NSC)-mediated following Ischemic Stroke (IS). Nonetheless, the mechanisms through which M2 influence NSC-mediated post-IS remain unclear. On other hand, microglia-derived small Extracellular Vesicles (M2-sEVs) exert phenomenal biological effects and play significant roles in cell-to-cell interactions, highlighting their potential involvement post-IS, forming basis of this study. M2-sEVs were first isolated from IL-4-stimulated microglia. For vivo tests, intravenously injected into mice every day for 14 days after transient Middle Cerebral Artery Occlusion (tMCAO). Following that, infarct volume neurological function, as well NSC proliferation Subventricular Zone dentate gyrus, migration, differentiation area, examined. vitro administered to subjected Oxygen-Glucose Deprivation (OGD) then reoxygenation, assessed. Finally, microRNA sequencing explore regulatory mechanisms. Our findings revealed that reduced increased score post-tMCAO. M2-sEV treatment promoted neuronal both vitro. Additionally, miR-93-5p miR-25-3p enrichment M2-sEVs. Inhibitors these miRNAs prevented TGFBR, PTEN, FOXO3 downregulation NSC, reversing M2-sEVs' beneficial on sensorimotor differentiation, protected against IS, at least partially, via delivering downregulate expression NSC.

Language: Английский

---

CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4865 - 4865

Published: April 29, 2024

Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both parenchyma and non-parenchymal tissue (meninges, perivascular space, choroid plexus) are richly populated in resident immune cells. The advent of more powerful tools multiplex immunophenotyping, such as single-cell RNA sequencing technique upscale multiparametric flow mass spectrometry, helped discriminating between infiltrating cells and, above all, different spectrum phenotypes distinguishing border-associated macrophages. Here, we focus our attention on innate players their primary role homeostasis pathological neuroinflammation neurodegeneration, two key interconnected aspects immunopathology multiple sclerosis.

Language: Английский

---

A microglia-containing cerebral organoid model to study early life immune challenges

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 26, 2024

Prenatal infections and activation of the maternal immune system have been proposed to contribute causing neurodevelopmental disorders (NDDs), chronic conditions often linked brain abnormalities. Microglia are resident cells play a key role in neurodevelopment. Disruption microglial functions can lead abnormalities increase risk developing NDDs. How as well fetal affect human neurodevelopment NDDs remains unclear. An important reason for this knowledge gap is fact that impact exposure prenatal factors has challenging study context. Here, we characterized model cerebral organoids (CO) with integrated microglia (COiMg). These express typical markers respond inflammatory stimuli. The presence influences organoid development, including cell density neural differentiation, regulates expression several ciliated mesenchymal markers. Moreover, COiMg without show similar but also distinct responses Additionally, IFN-γ induced significant transcriptional structural changes organoids, appear be regulated by microglia. Specifically, interferon-gamma (IFN-γ) was found alter genes autism. This provides valuable tool how perturbations processes.

Language: Английский

---

Therapeutic approaches to modulate the immune microenvironment in gliomas

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Oct. 23, 2024

Immunomodulatory therapies, including immune checkpoint inhibitors, have drastically changed outcomes for certain cancer types over the last decade. Gliomas are among cancers that seem limited benefit from these agents, with most trials yielding negative results. The unique composition of glioma microenvironment is culprits this lack efficacy. In recent years, several efforts been made to improve understanding microenvironment, aiming pave way novel therapeutic interventions. review, we discuss some main components macrophages, myeloid-derived suppressor cells, neutrophils and microglial as well lymphocytes. We then provide a comprehensive overview immunomodulatory agents currently in clinical development, namely oncolytic viruses, vaccines, cell-based therapies such CAR-T cells CAR-NK antibodies peptides.

Language: Английский

---

Single-cell Transcriptomic Profiling of Brains in Newborn Rats Following Hypoxic Ischemic Encephalopathy

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Background Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe neurological condition associated with high rates of mortality or long-term disability. Despite its clinical significance, the detailed cellular mechanisms underlying HIE remain unclear. Single-cell RNA sequencing (scRNA-seq) has emerged as powerful tool for investigating heterogeneity across development, aging, and disease processes. However, no scRNA-seq studies have yet addressed neonatal HIE. Methods We employed to examine during hyperacute (3 hours), acute (2 days), subacute (7 days) phases Uniform Manifold Approximation Projection (UMAP) was used visualize cell clustering. Differentially expressed genes (DEGs) were calculated identified using Seurat’s FindAllMarkers function, which enriched pathway analysis (GO, KEGG pathway, WikiPathways, Reactome Gene Sets). CytoTRACE v2 identify maturity state each type pseudotime performed Monocle v3. Results analyzed total 87,580 high-quality brain cells transcriptional changes In phase, we observed activation astrocytes in response reactive oxygen species, involvement microglia phagocytosis, Stat3-mediated ischemic responses oligodendrocyte precursor cells, an increase senescent lymphatic endothelial cells. found exacerbate inflammation impede while proliferated. Neuroblasts affected by metal ions, oligodendrocytes decreased. facilitated tissue repair, inflammatory highly expressing MHC II induced IL27 I interferon pathways expanded. Additionally, peripheral immune played vital roles Specifically, neutrophils infiltrated expanded throughout all post-HIE. Spp1^high macrophages, T plasmacytoid dendritic increased phases, B phase. Conclusion This study offers deep insights into molecular alterations key types following HIE, elucidating pathological processes involved. These findings significant implications developing effective strategies managing

Language: Английский

---