Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 921 - 921

Published: May 27, 2024

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality central nervous system (CNS). Astrocytes are vital orchestrating neuronal development by releasing synaptogenic molecules eliminating excessive synapses. They also modulate excitability contribute to CNS homeostasis, promoting survival clearance neurotransmitters, transporting metabolites, secreting trophic factors. highly heterogeneous respond injuries diseases through process known as reactive astrogliosis, which can both inflammation its resolution. Recent evidence has revealed remarkable alterations transcriptomes response several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic A2 neuroprotective astrocytes. However, due vast heterogeneity these it is limited classify them into only phenotypes. This review explores various physiological pathophysiological roles, potential markers, pathways that might be activated different astrocytic Furthermore, we discuss main neurodegenerative identify therapeutic strategies. Understanding underlying mechanisms differentiation imbalance population will allow identification specific biomarkers timely approaches diseases.

Language: Английский

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The role of astrocyte metabolic reprogramming in ischemic stroke (Review)

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 21, 2025

Ischemic stroke, a leading cause of disability and mortality worldwide, is characterized by the sudden loss blood flow in specific area brain. Intravenous thrombolysis with recombinant tissue plasminogen activator only approved pharmacological treatment for acute ischemic stroke; however, aforementioned has significant clinical limitations, thus there an urgent need development novel mechanisms therapeutic strategies stroke. Astrocytes, abundant versatile cells central nervous system, offer crucial support to neurons nutritionally, structurally physically. They also contribute blood‑brain barrier formation regulate neuronal extracellular ion concentrations. Accumulated evidence revealed involvement astrocytes regulation host neurotransmitter metabolism, immune response repair, different metabolic characteristics can process suggesting that targeted astrocyte reprogramming may prognosis In present review, current understanding multifaceted along its regulatory factors pathways, as well promote polarization balance, which hold promise immunometabolism‑targeted therapies were summarized.

Language: Английский

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The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Language: Английский

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The Crosstalk Between Immune Cells After Intracerebral Hemorrhage

Neuroscience, Journal Year: 2023, Volume and Issue: 537, P. 93 - 104

Published: Dec. 5, 2023

Language: Английский

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Immune cells in intracerebral hemorrhage

Brain Hemorrhages, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1031 - 1041

Published: June 3, 2024

Astrocytes are the most abundant type of glial cell in central nervous system. Upon injury and inflammation, astrocytes become reactive undergo morphological functional changes. Depending on their phenotypic classification as A1 or A2, contribute to both neurotoxic neuroprotective responses, respectively. However, this binary does not fully capture diversity astrocyte responses observed across different diseases injuries. Transcriptomic analysis has revealed that have a complex landscape gene expression profiles, which emphasizes heterogeneous nature reactivity. actively participate regulating system inflammation by interacting with microglia other types, releasing cytokines, influencing immune response. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is player reactivity impacts various aspects behavior, evidenced silico , vitro vivo results. In astrocytes, inflammatory cues trigger cascade molecular events, where nuclear factor-κB serves mediator pro-inflammatory responses. Here, we review heterogeneity mechanisms underlying activation. We highlight involvement pathways regulate reactivity, including PI3K/AKT/mammalian target rapamycin (mTOR), α v β 3 integrin/PI3K/AKT/connexin 43, Notch/PI3K/AKT pathways. While targeting inactivation PI3K/AKT cellular control prevent damage, evidence suggests activating could also yield beneficial outcomes. This dual function underscores its complexity brain modulation. importance employing astrocyte-exclusive models understand functions accurately these essential for clarifying behavior. findings should then be validated using ensure real-life relevance. highlights significance modulation preventing although further studies required comprehend role due varying factors such disease contexts. Specific strategies clearly necessary address variables effectively.

Language: Английский

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Dissecting the immune response of CD4⁺ T cells in Alzheimer’s disease

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract The formation of amyloid-β (Aβ) plaques is a neuropathological hallmark Alzheimer’s disease (AD), however, these pathological aggregates can also be found in the brains cognitively unimpaired elderly population. In that context, individual variations Aβ-specific immune response could key factors determine level Aβ-induced neuroinflammation and thus propensity to develop AD. CD4 + T cells are cornerstone coordinate effector functions both adaptive innate immunity. However, despite intensive research efforts, precise role during AD pathogenesis still not fully elucidated. Both pathogenic beneficial effects have been observed various animal models AD, as well humans with Although this functional duality simply attributed vast phenotype heterogeneity cell lineage, stage-specific effect proposed. Therefore, review, we summarized current understanding pathophysiology from aspect their antigen specificity, activation, characteristics. Such knowledge practical importance it paves way for immunomodulation therapeutic option treatment, given currently available therapies yielded satisfactory results.

Language: Английский

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Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 6, 2023

Abstract Alzheimer's disease (AD) affects various brain cell types, including astrocytes, which are the most abundant types in central nervous system (CNS). Astrocytes not only provide homeostatic support to neurons but also actively regulate synaptic signaling and functions become reactive response CNS insults through diverse pathways JAK/STAT, NF‐κB, GPCR‐elicited pathways. The advent of new technology for transcriptomic profiling at single‐cell level has led increasing recognition highly versatile nature astrocytes context‐dependent specificity astrocyte reactivity. In AD, have long been observed senile plaques recently suggested play a role AD pathogenesis progression. However, precise contributions remain elusive, targeting this complex population treatment poses significant challenges. review, we summarize current understanding reactivity its with particular focus on that promote heterogeneity astrocytes. Furthermore, explore potential implications development therapeutics AD. Our objective is shed light involvement offer insights into therapeutic targets strategies treating managing devastating neurodegenerative disorder.

Language: Английский

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Interleukin‐3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background Effective clearance of lipid‐rich debris by macrophages is critical for neural repair and regeneration after spinal cord injury (SCI). Interleukin‐3 (IL‐3) has been implicated in programming microglia to cluster clear pathological aggregates neurodegenerative disease. Yet, the influence IL‐3 on lipid post‐SCI not well characterized. Methods We established a mouse model compression investigate role IL‐3. Blockage was achieved through intrathecal delivery an IL‐3‐neutralizing antibody, while activation augmented via situ injection recombinant into lesion site immediately post‐SCI. Immunofluorescence staining performed determine IL‐3Rα sources distribution, droplet accumulation, neuron preservation, axon SCI. The Basso Mouse Scale (BMS) footprint analysis were employed evaluate locomotor function recovery. Results found that expression significantly upregulated post‐SCI, peaking at 14 days post‐injury (dpi) persisting until 28 dpi. Notably, primarily secreted astrocytes surrounding epicenter. Correspondingly, predominantly observed within core, also elevating Neutralization led increased along with markedly widespread decreased neuronal survival, resulting severe motor deficits compared controls. Conversely, reduced accumulation macrophages, preserved neurons, promoted regeneration, ultimately contributed recovery Conclusion Our findings shed light modulating macrophage phagocytic activity suggest IL‐3/IL‐3Rα pathway may be potential therapeutic target enhancing functional

Language: Английский

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