Neuropeptides, Journal Year: 2025, Volume and Issue: 111, P. 102516 - 102516
Published: March 12, 2025
Language: Английский
Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 80 - 99
Published: Jan. 6, 2024
Language: Английский
Citations
17
Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)
Published: Nov. 17, 2022
Abstract Microglia represent the first line of immune feedback in brain. Beyond surveillance, they are essential for maintaining brain homeostasis. Recent research has revealed microglial cells' spatiotemporal heterogeneity based on their local and time-based functions trauma or disease when homeostasis is disrupted. Distinct "microglial signatures" have been recorded physiological states injuries, with discrete sometimes overlapping pro- anti-inflammatory functions. involved neurological repair processes, such as neurovascular unit restoration synaptic plasticity, manage extent damage due to phenotype switching. The versatility cellular phenotypes beyond classical M1/M2 classification, well double-edge actions microglia neurodegeneration, indicate need further exploration cell dynamics contribution neurodegenerative processes. This review discusses homeostatic different subsets focusing neuropathological conditions. Also, we address feasibility targeting a therapeutic strategy diseases.
Language: Английский
Citations
60
Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)
Published: Dec. 17, 2022
Amongst risk alleles associated with late-onset Alzheimer's disease (AD), those that converged on the regulation of microglia activity have emerged as central to progression. Yet, how canonical amyloid-β (Aβ) and tau pathologies regulate subtypes during progression AD remains poorly understood.We use single-cell RNA-sequencing profile from mice exhibiting both Aβ across We identify novel are induced in response a disease-stage-specific manner. To validate observation mouse models, we also generated snRNA-Seq dataset human superior frontal gyrus (SFG) entorhinal cortex (ERC) at different Braak stages.We show early-stage disease, interferon signaling induces subtype termed Early-stage AD-Associated Microglia (EADAM) pathologies. During late-stage second Late-stage (LADAM) is detected. While similar observed other models neurodegenerative magnitude composition gene signatures found EADAM LADAM distinct, suggesting necessity elicit their emergence. Importantly, pattern EADAM- LADAM-associated expression brains, early (Braak II)- or late VI/V)- stage respectively. Furthermore, several Siglec genes selectively expressed either LADAM. Siglecg white-matter-associated LADAM, Siglec-10, orthologue Siglecg, progressively elevated an AD-stage-dependent manner but not shown non-AD tauopathy.Using scRNA-Seq bearing and/or pathologies, by combination stage-specific Our findings suggest required for induction In addition, revealed Siglecs biomarkers potential therapeutic targets.
Language: Английский
Citations
40
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: June 2, 2023
Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer’s disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading dementia and death, characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal neurofibrillary tangles (NFTs) consisting altered hyperphosphorylated tau protein. Both have been widely studied pharmacologically targeted for many years, without significant results. In 2022, positive data on monoclonal antibodies targeting Aβ, donanemab lecanemab, followed 2023 FDA accelerated approval lecanemab publication final results phase III Clarity AD study, strengthened hypothesis causal role Aβ in pathogenesis AD. However, magnitude clinical effect elicited drugs limited, suggesting that additional mechanisms may contribute disease. Cumulative studies shown inflammation as one main contributors recognition specific neuroinflammation synergic with NFTs cascades. The present review provides an overview investigational are trials. Moreover, their action, positioning cascade events occur brain throughout potential benefit/limitation strategy discussed highlighted well. addition, latest patent requests inflammation-targeting therapeutics be developed will also discussed.
Language: Английский
Citations
26
The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(2)
Published: Jan. 16, 2024
Aducanumab, an anti-amyloid immunotherapy for Alzheimer’s disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect aducanumab treatment withdrawal on neuritic dystrophy, astrocytes, microglia in APP/PS1 amyloid mouse model. found that reductions dystrophy during acute were accompanied by microglial astrocytic activation, recruitment to plaques adoption aducanumab-specific pro-phagocytic pro-degradation transcriptomic signature, indicating a role aducanumab-mediated Aβ clearance. Reductions sustained 15 but 30 wk after discontinuation, reaccumulation coincided with loss signature failure reactivate. This suggests despite initial benefit from treatment, unable respond later restrain reaccumulation, making further studies amyloid-directed crucial assessing safety efficacy.
Language: Английский
Citations
12
Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 102(3), P. 287 - 311
Published: Jan. 6, 2024
Language: Английский
Citations
9
Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)
Published: March 25, 2024
Language: Английский
Citations
9
Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105848 - 105848
Published: Aug. 13, 2024
Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated relationship between T2D-related and activation polarization of microglia. This review summarizes potential mechanisms microglial context T2D. It discusses inflammatory responses, neuronal apoptosis, amyloid-β deposition, abnormal phosphorylation Tau protein mediated by polarization, exploring connections from multiple perspectives. Additionally, this provides references for future treatment targeting microglia clinical translation.
Language: Английский
Citations
9
Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106817 - 106817
Published: Jan. 1, 2025
S100 calcium-binding protein A9 (S100A9, also known as calgranulin B) is expressed and secreted by myeloid cells under inflammatory conditions, S100A9 can amplify inflammation. There a large increase in expression the brains of patients with neurodegenerative diseases, such Alzheimer's disease, has been suggested to contribute neurodegeneration, but mechanisms are unclear. Here we investigated effects extracellular recombinant on microglia, neurons synapses primary rat brain neuronal-glial cell cultures. Incubation cultures 250-500 nM caused neuronal loss without signs apoptosis or necrosis, accompanied exposure "eat-me" signal - phosphatidylserine neurons. activation microglial inflammation evidenced an number, morphological changes, release pro-inflammatory cytokines, increased phagocytic activity. At lower concentrations, 10-100 induced synaptic Depletion microglia from prevented S100A9-induced loss, indicating that was mediated microglia. These results suggest may neurodegeneration activating phagocytosis, resulting This further suggests possibility be reduced targeting
Language: Английский
Citations
1
Published: Jan. 1, 2025
Language: Английский
Citations
1