Understanding mechanisms of antioxidant action in health and disease

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(1), P. 13 - 33

Published: Sept. 15, 2023

Language: Английский

---

Oxidative stress and inflammation cause auditory system damage via glial cell activation and dysregulated expression of gap junction proteins in an experimental model of styrene-induced oto/neurotoxicity

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 4, 2024

Abstract Background Redox imbalance and inflammation have been proposed as the principal mechanisms of damage in auditory system, resulting functional alterations hearing loss. Microglia astrocytes play a crucial role mediating oxidative/inflammatory injury central nervous system; however, glial cells is still elusive. Objectives Here we investigated glial-mediated responses to toxic peripheral structures pathway, i.e., cochlea cortex (ACx), rats exposed styrene, volatile compound with well-known oto/neurotoxic properties. Methods Male adult Wistar were treated styrene (400 mg/kg daily for 3 weeks, 5/days week). Electrophysiological, morphological, immunofluorescence molecular analyses performed both ACx evaluate underlying styrene-induced oto/neurotoxicity system. Results We showed that insult induced by increases oxidative stress ACx. This was associated macrophages cell activation, increased expression inflammatory markers (i.e., pro-inflammatory cytokines chemokine receptors) connexin (Cxs) pannexin (Panx) expression, likely responsible dysregulation microglia/astrocyte network. Specifically, found downregulation Cx26 Cx30 cochlea, high level Cx43 Panx1 Conclusions Collectively, our results provide novel evidence on immune activation system at levels, also involving gap junction networks. Our data suggest targeting connexin/pannexin might be useful attenuate

Language: Английский

---

Targeting Microglia in Alzheimer’s Disease: Pathogenesis and Potential Therapeutic Strategies

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 833 - 833

Published: July 11, 2024

Microglia, as resident macrophages in the central nervous system, play a multifunctional role pathogenesis of Alzheimer’s disease (AD). Their clustering around amyloid-β (Aβ) deposits is core pathological feature AD. Recent advances single-cell RNA sequencing (scRNA-seq) and single-nucleus (snRNA-seq) have revealed dynamic changes microglial phenotypes over time across different brain regions during aging AD progression. As advances, microglia primarily exhibit impaired phagocytosis Aβ tau, along with release pro-inflammatory cytokines that damage synapses neurons. Targeting has emerged potential therapeutic approach for Treatment strategies involving can be broadly categorized into two aspects: (1) enhancing function: This involves augmenting their phagocytic ability against cellular debris (2) mitigating neuroinflammation: Strategies include inhibiting TNF-α signaling to reduce neuroinflammatory response triggered by microglia. Clinical trials exploring microglia-related approaches treatment garnered attention. Additionally, natural products show promise beneficial effects suppressing inflammatory responses. Clarifying dynamics, understanding roles, novel will advance our fight

Language: Английский

---

Decoding the role of the CCL2/CCR2 axis in Alzheimer’s disease and innovating therapeutic approaches: Keeping All options open

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 135, P. 112328 - 112328

Published: May 25, 2024

Language: Английский

---

The role of integrins in brain health and neurodegenerative diseases

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(3), P. 151441 - 151441

Published: July 6, 2024

Integrins are heterodimeric membrane proteins expressed on the surface of most cells. They mediate adhesion and signaling processes relevant for a wealth physiological processes, including nervous system development function. Interestingly, integrins also recognized therapeutic targets inflammatory diseases, such as multiple sclerosis. Here, we discuss role in brain function, well neurodegenerative diseases affecting (Alzheimer's disease, sclerosis, stroke). Furthermore, targeting these receptors brain.

Language: Английский

---

Role of TREM2 in immune and neurological diseases: Structure, function, and implications

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113286 - 113286

Published: Oct. 7, 2024

Language: Английский

---

Decoding Microglial Polarization and Metabolic Reprogramming in Neurodegenerative Diseases: Implications for Disease Progression and Therapy

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

As the resident macrophages of brain, microglia are crucial immune cells specific to central nervous system (CNS). They constantly surveil their surroundings and trigger immunological reactions, playing a key role in various neurodegenerative diseases (ND). illnesses progress, exhibit multiple phenotypes. Traditionally, have been classified into two main phenotypes upon activation: pro-inflammatory M1 polarization anti-inflammatory M2 polarization. However, this classification is now considered overly simplistic, as it unable fully convey intricacy diversity inflammatory response. Immune regulatory factors, such chemokines secreted by microglia, essential for modulating brain development, maintaining neural milieu, orchestrating responses injury, along with subsequent repair processes. recent years, significance metabolic reprogramming both physiological microglial activity ND has also become increasingly recognized. Upon activation-triggered infection, or ND-microglia typically modify processes transitioning from oxidative phosphorylation (OXPHOS) glycolysis. This shift facilitates rapid energy production but may enhance responses. review seeks summarize function involvement ND.

Language: Английский

---

A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 8, 2025

Although phobia is a common psychiatric disorder, the underlying biological mechanisms have not been fully elucidated. Complex immune-brain interactions that affect neural development, survival, and function may causal therapeutic implications in illnesses. In this study, relationships between immune cell traits were analysed using Mendelian randomization to explore mechanisms. Based on publicly-available genetic data, two-sample MR analysis was used determine relationship 731 risk of developing phobias. Sensitivity analyses conducted verify robustness, heterogeneity, horizontal pleiotropy results. After forward reverse analyses, false discovery rate (FDR) corrections performed. No significant associations phobias identified. adjusting FDR threshold, social affected two traits: CD39 granulocytes (β = 9.0347, 95% confidence interval (CI) 4.4802-13.5891, P 0.0001, 0.0738), CD11c 7.7976, CI 3.4616-12.1336, 0.0004, 0.1547). Three specific phobias: CD4 + CD8dim T %leukocyte (odds ratio (OR) 0.9985, 0.9976-0.9993, 0.0006, 0.1373), CD45 CD33 HLA DR CD14dim (OR 0.9977, 0.9964-0.9990, CD8 CD28 CD45RA CD8br 0.9990, 0.9985-0.9996, 0.0003, 0.1373). Two agoraphobia: CD3 resting regulatory cells (Tregs) 1.0010, 95 CI%=1.0005-1.0015, 0.0596) CD33br 0.9993, CI%=0.9990-0.9997, 0.0002, 0.0596). Immune closely related screened out through genomics, which provides reference for subsequent research system-phobia interaction.

Language: Английский

---

Molecular and functional characteristics of receptor-interacting protein kinase 1 (RIPK1) and its therapeutic potential in Alzheimer's disease

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(12), P. 103750 - 103750

Published: Aug. 24, 2023

Language: Английский

---

Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication

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

Published: Sept. 2, 2024

Abstract Effective communication between different cell types is essential for brain health, and dysregulation of this process leads to neuropathologies. Brain glial cells, including microglia astrocytes, orchestrate immune defense neuroimmune responses under pathological conditions during which interglial indispensable. Our appreciation the complexity these processes rapidly increasing due recent advances in molecular biology techniques, have identified numerous phenotypic states both astrocytes. This review focuses on microglia-to-astrocyte facilitated by secreted modulators. The combinations interleukin (IL)-1α, tumor necrosis factor (TNF), plus complement component C1q as well IL-1β TNF are already well-established microglia-derived stimuli that induce reactive phenotypes However, given large number inflammatory mediators distinct functional recognized it can be hypothesized many more intercellular signaling molecules exist. identifies following group cytokines gliotransmitters that, while not established yet, known released elicit astrocytes: IL-10, IL-12, IL-18, transforming growth (TGF)-β, interferon (IFN)-γ, C–C motif chemokine ligand (CCL)5, adenosine triphosphate (ATP), l -glutamate, prostaglandin E2 (PGE2). mechanisms engaged reveals complex, partially overlapping pathways implicated Additionally, lack human-specific studies a significant knowledge gap. Further research warranted, could discover novel signaling-targeted therapies diverse neurological disorders.

Language: Английский

---