TAMing Gliomas: Unraveling the Roles of Iba1 and CD163 in Glioblastoma DOI Open Access

Haneya Fuse,

Yuqi Zheng, Islam Alzoubi

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1457 - 1457

Published: April 26, 2025

Gliomas, the most common type of primary brain tumor, are a significant cause morbidity and mortality worldwide. Glioblastoma, highly malignant subtype, is particularly common, aggressive, resistant to treatment. The tumor microenvironment (TME) gliomas, especially glioblastomas, characterized by distinct presence tumor-associated macrophages (TAMs), which densely infiltrate hallmark these tumors. This macrophage population comprises both tissue-resident microglia as well derived from walls blood vessels stream. Ionized calcium-binding adapter molecule 1 (Iba1) CD163 established cellular markers that enable identification functional characterization cells within TME. review provides an in-depth examination roles Iba1 in with focus on TAM activation, migration, immunomodulatory functions. Additionally, we will discuss how recent advances AI-enhanced cell visualization techniques have begun transform analysis TAMs, promising unprecedented precision their providing new insights into appear unique shared glioma pathobiology, potential be targeted through different molecular mechanisms. We therapeutic based available preclinical (experimental) clinical (human tissue-based) evidence.

Language: Английский

Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets DOI Creative Commons
Chao Gao, Jingwen Jiang, Yuyan Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 22, 2023

Abstract Microglia activation is observed in various neurodegenerative diseases. Recent advances single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified specific states correlate pathological hallmarks are associated functions. both exert protective function by phagocytosing clearing protein aggregates play detrimental roles due to excessive uptake of aggregates, which would lead microglial phagocytic ability impairment, neuroinflammation, eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes into a pro-inflammatory phenotype accelerates disease progression. also act as mobile vehicle propagate aggregates. Extracellular vesicles released from autophagy impairment all contribute progression Thus, enhancing phagocytosis, reducing microglial-mediated inhibiting exosome synthesis secretion, promoting conversion considered be promising strategies for the therapy Here we comprehensively review biology diseases, including Alzheimer’s disease, Parkinson’s multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia Lewy bodies Huntington’s disease. We summarize possible microglia-targeted interventions treatments against diseases preclinical clinical evidence cell experiments, animal studies, trials.

Language: Английский

Citations

441
Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer's disease DOI Creative Commons

Zhijun He,

Xiaoqian Li, Zi Wang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 66, P. 102848 - 102848

Published: Aug. 12, 2023

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) peptides and dysfunction mitochondrion, which result in neuronal apoptosis ultimately cognitive impairment. Inhibiting Aβ generation repairing mitochondrial damage are prominent strategies AD therapeutic treatment. Luteolin, flavonoid compound, exhibits anti-inflammatory neuroprotective properties mice. However, it still unclear whether luteolin has any effect on pathology dysfunction. In this study, beneficial underlying mechanism were investigated triple transgenic (3 × Tg-AD) mice primary neurons. Our study showed that supplement significantly ameliorated memory impairment exerted neuroprotection inhibiting generation, reducing apoptosis. Further research revealed could directly bind with peroxisome proliferator-activated receptor gama (PPARγ) to promote its expression function. culture hippocampus-derived neurons, addition PPARγ antagonist GW9662 or knockdown siRNA eliminate pathologies. summary, work for first time effectively improved deficits 3 Tg-AD inhibited Aβ-induced oxidative stress, via PPARγ-dependent mechanism. Hence, potential serve as agent against AD.

Language: Английский

Citations

76
Biomimetic Nanovesicles as a Dual Gene Delivery System for the Synergistic Gene Therapy of Alzheimer’s Disease DOI

Sujun Jiang,

Guoen Cai, Zhimin Yang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(18), P. 11753 - 11768

Published: April 22, 2024

The association between dysfunctional microglia and amyloid-β (Aβ) is a fundamental pathological event increases the speed of Alzheimer's disease (AD). Additionally, pathogenesis AD intricate single drug may not be enough to achieve satisfactory therapeutic outcome. Herein, we reported facile effective gene therapy strategy for modulation function intervention Aβ anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). codelivery β-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) TREM2 plasmid (pTREM2) efficiently penetrate blood-brain barrier enhance accumulation at lesions with help exosomes homing ability angiopep-2 peptides. Specifically, an upregulation expression can reprogram from pro-inflammatory M1 phenotype anti-inflammatory M2 while also restoring its capacity phagocytose nerve repair function. In addition, reduces production plaques source knocking out BACE1 gene, which expected further effect AD. in vivo study suggests that TSEL through synergistic two drugs ameliorate APP/PS1 mice cognitive impairment regulating activated microglial phenotype, reducing Aβ, preventing retriggering neuroinflammation. This employs delivery dual nucleic acids, achieving AD, thus offering more options treatment

Language: Английский

Citations

30
Microneedle-mediated nose-to-brain drug delivery for improved Alzheimer's disease treatment DOI

Shuyao Ruan,

Jiaqi Li, Hang Ruan

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 366, P. 712 - 731

Published: Jan. 21, 2024

Language: Английский

Citations

28
A New Strategy for the Regulation of Neuroinflammation: Exosomes Derived from Mesenchymal Stem Cells DOI Creative Commons
Ying Ge, Jingjing Wu, Li Zhang

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Feb. 19, 2024

Abstract Neuroinflammation is an important pathogenesis of neurological diseases and causes a series physiopathological changes, such as abnormal activation glial cells, neuronal degeneration death, disruption the blood‒brain barrier. Therefore, modulating inflammation may be therapeutic tool for treating diseases. Mesenchymal stem cells (MSCs), pluripotent have great potential due to their regenerative ability, immunity, ability regulate inflammation. However, recent studies shown that MSC-derived exosomes (MSC-Exos) play major role in this process key neuroprotection by regulating neuroglia. This review summarizes progress made neuroinflammation focusing on mechanisms which MSC-Exos are involved regulation through signaling pathways TLR, NF-κB, MAPK, STAT, NLRP3 provide some references subsequent research therapy. Graphical Exosomes derived from MSCs exhibit neuroprotective effects mitigating triggered cells.

Language: Английский

Citations

20
Chemerin-9 is neuroprotective in APP/PS1 transgenic mice by inhibiting NLRP3 inflammasome and promoting microglial clearance of Aβ DOI Creative Commons
Jiawei Zhang, Yaxuan Zhang, Lan Liu

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 8, 2025

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder worldwide, and microglia are thought to play central role in neuroinflammatory events occurring AD. Chemerin, an adipokine, has been implicated inflammatory diseases nervous system disorders, yet its precise function on microglial response AD remains unknown. The APP/PS1 mice were treated with different dosages of chemerin-9 (30 60 µg/kg), bioactive nonapeptide derived from chemerin, every other day for 8 weeks consecutively. primary mouse stimulated by amyloid beta 42 (Aβ42) oligomers followed treatment vitro. ChemR23 inhibitor α-NETA was further used investigate whether the effects ChemR23-dependent. We found that expression chemerin increased Intriguingly, significantly ameliorated Aβ deposition cognitive impairment mice, decreased proinflammatory activity phagocytic activity. Similarly, chemerin-9-treated showed ability NLRP3 inflammasome activation. However, abolished neuroprotective chemerin-9. Collectively, our data demonstrate ameliorates deficits transgenic boosting phenotype.

Language: Английский

Citations

2
Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation DOI Creative Commons
Xiang Li,

Qingyong Ding,

Xinxin Wan

et al.

Behavioral and Brain Functions, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 8, 2025

Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that the leading cause of dementia. The underlying mechanisms AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has exhibited to play crucial role in pathogenesis AD. Additionally, disruption gut microbiota found be associated with AD, fecal transplantation (FMT) emerged as potential therapeutic approach. However, precise mechanism FMT treatment remains elusive. In this study, was performed transplanting from healthy wild-type mice into APP/PS1 (APPswe, PSEN1dE9) assess effectiveness mitigating AD-associated inflammation reveal its action. results demonstrated improved cognitive function reduced expression levels factors regulating TLR4/MyD88/NF-κB signaling pathway mice, which accompanied restoration microbial dysbiosis. These findings suggest ameliorate symptoms delay progression mice.

Language: Английский

Citations

2
Targeting glycogen synthase kinase-3β for Alzheimer's disease: Recent advances and future Prospects DOI

Zimeng Cheng,

Tianyue Han,

Jingtong Yao

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 265, P. 116065 - 116065

Published: Dec. 20, 2023

Language: Английский

Citations

17
The emerging role of brain neuroinflammatory responses in Alzheimer’s disease DOI Creative Commons

Mandana Amelimojarad,

Melika Amelimojarad,

Xiaonan Cui

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: July 3, 2024

As the most common cause of dementia, Alzheimer’s disease (AD) is characterized by neurodegeneration and synaptic loss with an increasing prevalence in elderly. Increased inflammatory responses triggers brain cells to produce pro-inflammatory cytokines accelerates Aβ accumulation, tau protein hyper-phosphorylation leading neurodegeneration. Therefore, this paper, we discuss current understanding how inflammation affects activity induce AD pathology, biomarkers possible therapies that combat for AD.

Language: Английский

Citations

8
The neuroinflammatory role of microglia in Alzheimer's disease and their associated therapeutic targets DOI Creative Commons

Melika Amelimojarad,

Mandana AmeliMojarad

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Abstract Introduction Alzheimer's disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid‐β (Aβ) accumulation, hyperphosphorylation tau protein, neurofibrillary tangles (NFTs) in brain are considered to be initiating factors AD. However, this hypothesis falls short explaining many aspects AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role pathophysiology causes neurodegeneration over‐activating microglia releasing inflammatory mediators. Methods PubMed, Web Science, EMBASE, MEDLINE were used for searching summarizing all recent publications related inflammation its association with disease. Results Our review shows how dysregulation influences pathology as well roles neuroinflammation, possible microglia‐associated therapeutic targets, top neuroinflammatory biomarkers, anti‐inflammatory drugs combat inflammation. Conclusion In conclusion, microglial reactions important pathogenesis need discussed more detail promising strategies.

Language: Английский

Citations

8