Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

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

Published: March 7, 2023

Microglia are the principal resident immune cells in central nervous system (CNS) and play important roles development of CNS disorders. In recent years, there have been significant developments our understanding microglia, we now greater insight into temporal spatial patterns microglia activation a variety disorders, as well interactions between neurons. A signaling pathways implicated. However, to date, all published clinical trials failed demonstrate efficacy over placebo. This review summarizes results studies attempts provide mechanistic view activation, inflammation, tissue repair,

Language: Английский

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Dual-3DM³AD: Mixed Transformer Based Semantic Segmentation and Triplet Pre-Processing for Early Multi-Class Alzheimer’s Diagnosis

IEEE Transactions on Neural Systems and Rehabilitation Engineering, Journal Year: 2024, Volume and Issue: 32, P. 696 - 707

Published: Jan. 1, 2024

Alzheimer's Disease (AD) is a widespread, chronic, irreversible, and degenerative condition, its early detection during the prodromal stage of utmost importance. Typically, AD studies rely on single data modalities, such as MRI or PET, for making predictions. Nevertheless, combining metabolic structural can offer comprehensive perspective staging analysis. To address this goal, paper introduces an innovative multi-modal fusion-based approach named Dual-3DM ³ -AD. This model proposed accurate diagnosis by considering both PET image scans. Initially, we pre-process images in terms noise reduction, skull stripping 3D conversion using Quaternion Non-local Means Denoising Algorithm (QNLM), Morphology function Block Divider Model (BDM), respectively, which enhances quality. Furthermore, have adapted Mixed-transformer with Furthered U-Net performing semantic segmentation minimizing complexity. -AD consisted multi-scale feature extraction module extracting appropriate features from segmented images. The extracted are then aggregated Densely Connected Feature Aggregator Module (DCFAM) to utilize features. Finally, multi-head attention mechanism dimensionality softmax layer applied multi-class diagnosis. compared several baseline approaches help performance metrics. final results unveil that work achieves 98% accuracy, 97.8% sensitivity, 97.5% specificity, 98.2% f-measure, better ROC curves, outperforms other existing models multiclass

Language: Английский

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Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 11, 2025

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Multiple Sclerosis (MS), and Huntington’s (HD), although distinct in their clinical manifestations, share a common hallmark: disrupted neuroinflammatory environment orchestrated by dysregulation of neuroglial intercellular communication. Neuroglial crosstalk is physiologically ensured extracellular mediators the activity connexins (Cxs), forming proteins gap junctions (Gjs) hemichannels (HCs), which maintain intracellular homeostasis. However, accumulating evidence suggests that Cxs can also act pathological pore conditions, thereby contributing to neurodegenerative phenomena synaptic dysfunction, oxidative stress, ultimately cell death. This review explores mechanistic insights Cxs-mediated communication progression diseases discusses therapeutic potential targeting restore cellular

Language: Английский

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Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 6950 - 6950

Published: June 22, 2022

Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have well documented. The health garlic likely arise from wide variety components, possibly working synergistically. Garlic extracts, especially aged extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant neuroprotective activities. In light these effects, components examined experimental models Alzheimer’s disease (AD), most common form dementia without therapy, growing concern aging societies. With aim offering an updated overview, this paper reviews chemical composition, metabolism bioavailability compounds. addition, it provides overview signaling mechanisms triggered by derivatives, focus on allicin AGE, to improve learning memory.

Language: Английский

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Brain resident microglia in Alzheimer’s disease: foe or friends

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(5), P. 2781 - 2800

Published: Aug. 21, 2024

Language: Английский

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Eicosanoid signaling in neuroinflammation associated with Alzheimer's disease

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 976, P. 176694 - 176694

Published: May 29, 2024

Language: Английский

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Dysfunctional microglia and tau pathology in Alzheimer’s disease

Reviews in the Neurosciences, Journal Year: 2022, Volume and Issue: 34(4), P. 443 - 458

Published: Oct. 27, 2022

Extensive human studies and animal models show that chronic immune system stimulation involving microglia, inflammasome, complement activation, synthesis of cytokines, reactive oxygen species exacerbates neurodegeneration in Alzheimer's disease (AD) other tauopathies. Abnormalities tau, Aβ, microglial activation are frequently observed dementia patients indicate these elements may work concert to cause cognitive impairment. Contradicting reports from postmortem demonstrating the presence Aβ aggregates brains cognitively healthy individuals, as well investigations, tau aggregation is more strongly associated with synapse loss, neurodegeneration, decline than amyloid pathology. Tau association microtubules' surface promotes their growth maintains assembly, dynamicity, stability. In contrast, reduced affinity hyperphosphorylated mislocalized microtubules leads axonal deficits neurofibrillary tangles (NFTs). Loss neuroprotective phagocytic functions, indicated by faulty clearance plaques, correlations between tangle spread, all demonstrate critical involvement malfunctioning microglia driving propagation. This review discusses recent on contribution cells development progression The detailed study pathogenic mechanisms involved interactions neuroinflammation spread identifying targets for efficacious treatment strategies AD.

Language: Английский

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Radiotherapy for non-cancer diseases: benefits and long-term risks

International Journal of Radiation Biology, Journal Year: 2024, Volume and Issue: 100(4), P. 505 - 526

Published: Jan. 5, 2024

Purpose The discovery of X-rays was followed by a variety attempts to treat infectious diseases and various other non-cancer with ionizing radiation, in addition cancer. There has been recent resurgence interest the use such radiotherapy for diseases. Non-cancer which currently proposed include refractory ventricular tachycardia, neurodegenerative (e.g. Alzheimer's disease dementia), Coronavirus Disease 2019 (COVID-19) pneumonia, all ongoing clinical studies that deliver radiation doses 0.5–25 Gy single fraction or multiple daily fractions. In effects, historical indications predominantly used some countries Germany) osteoarthritis degenerative bones joints. This narrative review gives an overview biological rationale preclinical diseases, discusses plausibility rationale, considers long-term risks cancer

Language: Английский

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Spatiotemporal Dysregulation of Neuron–Glia Related Genes and Pro-/Anti-Inflammatory miRNAs in the 5xFAD Mouse Model of Alzheimer’s Disease

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

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Antagonizing Il10 and Il4 signaling via intracerebral decoy receptor expression attenuates Aβ accumulation

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 7, 2025

Abstract Multiple lines of evidence indicate that immune signaling can impact the pathological progression in Alzheimer’s disease (AD), including amyloid deposition, tau aggregation, synaptic pathology and neurodegenerative trajectory. In earlier studies, we reported intracerebral expression anti-inflammatory cytokines, Interleukin-10 (Il10) Interleukin-4 (Il4), increased β (Aβ) burden TgCRND8 mice, a preclinical model AD-type amyloidosis. As both receptor (IL10R) (IL4R) are upregulated an age-progressive manner rodent models AD specific regions human brains, hypothesized decoy strategy specifically targeting Il10 Il4 could have disease-modifying effect. We derivatized ectodomains mouse Il10R (sIl10R) Il4R (sIl4R) into corresponding recombinant solubilized forms delivered these intracranially neonatal mice or hippocampally adult with pre-existing Aβ deposits. AAV-mediated sIl10R sIl4R robustly attenuated when expressed neonatally while hippocampus injection cohort, AAV-sIl4R, but not sIl10R, reduced burden. had opposing effects on microglial astrocyte proliferation, generally reducing gliosis. RNAseq analysis showed likely acts as checkpoint inhibitor show unexpected impacts genes related to circadian rhythm. Notably, neither nor altered two transgenic models, despite robust glial proliferation. Together, data reveal mediated physiological beneficially deposition thus represent novel immunomodulatory approaches for therapy.

Language: Английский

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