Inhibition of adenosine/A2A receptor signaling suppresses dermal fibrosis by enhancing fatty acid oxidation DOI Creative Commons
Xiaoye Zhang,

Jinjian Sun,

Jia Guo

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 29, 2025

Skin fibrosis presents a major challenge for clinicians treating conditions like systemic sclerosis (SSc) due to its progressive course and limited treatment options. While the role of metabolism in has gained increasing attention, crucial alterations metabolic pathway underlying signaling interconnections regulating SSc-related skin remain largely elusive. Metabolomic analysis was performed on plasma samples from 35 SSc patients identify alterations. In bleomycin (BLM)- hypochlorous acid (HOCL)-induced mouse models, we assessed impact global A2a receptor knockout fibrosis. Single-cell RNA sequencing utilized investigate A2A fibroblasts during fibrotic challenge. Human dermal were used vitro experiments, employing Seahorse assays, assess relationship between fatty oxidation (FAO). Finally, fibroblast-specific conditional mice test effects specifically targeting fibroblasts. Adenosine-centered nucleotide elevated patients. Mechanistically, by stimulating with key pathogenic cytokines associated SSc, observed significant changes adenosine expression response IL-1β. Immunofluorescence revealed upregulation Further, significantly attenuated both BLM- HOCL-induced models. A2a-deficient following sequencing, assays experiments showed that inhibition promotes FAO upregulating CPT1A via suppressing CREB phosphorylation, alleviating human primary Furthermore, targeted intervention improves outcomes increases BLM-induced model. Our study highlights interplay metabolism-A2A axis SSc-associated fibrosis, suggesting A2A-FAO offers promising therapeutic strategy

Language: Английский

Noradrenergic system in the pathogenesis of age-dependent neurodegeneration DOI
Robert Zorec

Ageing & Longevity, Journal Year: 2025, Volume and Issue: 1.2025, P. 28 - 34

Published: Jan. 28, 2025

Ageing is a key factor in the development of cognitive decline and neurodegeneration, including Alzheimer’s disease (AD), most common form dementia diagnosed. In 2023 US Federal Drug Administration (FDA) approved new drug (Lecanemab, Leqembi) to treat AD that very moderately slows down early-stage (van Dyck et al., 2023). Donanemab (Kisunla, Eli Lilley), acting similarly lecanemab, was by FDA 2024 US, but not yet European Medicines Agency (EMA) EU. The mechanism action both these monoclonal antibodies similar aducanumab (Aduhelm), conditionally for 2021 (but subsequently discontinued producer), on reducing β-amyloid deposits (Sevigny 2016; van However, trials all revealed significant adverse events (brain swelling or brain bleeding); hence treatment neurodegeneration general remains an important unmet medical need, affecting millions people worldwide. Here I discuss role noradrenergic system innervating spinal cord, consisting nucleus locus coeruleus (LC), which appears be vulnerable structure central nervous (CNS) ageing-related factors, leading early LC demise impairments. Therefore, propose understanding noradrenaline cells, particular astrocytes, homeostasis-providing exhibit high density adrenergic receptors, future strategy develop drugs mitigate decline. Keywords: ageing; noradrenaline; adrenoceptors; coeruleus; neuroglia, astrocytes

Language: Английский

Citations

1
Single Mesenchymal Stromal Cell Migration Tracking into Glioblastoma Using Photoconvertible Vesicles DOI Creative Commons
Olga A. Sindeeva, Polina A. Demina, Zhanna V. Kozyreva

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(14), P. 1215 - 1215

Published: July 17, 2024

Reliable cell labeling and tracking techniques are imperative for elucidating the intricate ambiguous interactions between mesenchymal stromal cells (MSCs) tumors. Here, we explore fluorescent photoconvertible nanoengineered vesicles to study mMSC migration in brain These 3 μm sized made of carbon nanoparticles, Rhodamine B (RhB), polyelectrolytes readily internalized by cells. The dye undergoes photoconversion under 561 nm laser exposure with a fluorescence blue shift upon demand. optimal irradiation duration was 0.4 ms, which provided maximal signal label without excessive on Vesicles modified an extra polymer layer demonstrated enhanced intracellular uptake remarkable effects viability, motility, or proliferation. ratio 20 per determined. Moreover, individual mMSCs within 2D 3D glioblastoma (EPNT-5) colonies over 2 days vivo tumor settings 7 were traced. Our provides robust nanocomposite platform investigating MSC–tumor dynamics offers insights into envisaged therapeutic strategies. Photoconvertible also present indispensable tool studying complex fundamental processes cell–cell wide range problems biomedicine.

Language: Английский

Citations

5
Metabolic dysregulation in Huntington's disease: Neuronal and glial perspectives DOI Creative Commons
Ching‐Pang Chang,

Ching-Wen Wu,

Yijuang Chern

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: unknown, P. 106672 - 106672

Published: Sept. 1, 2024

Language: Английский

Citations

4
Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities DOI
Yuqing Liu, Lei Wu, Weijun Peng

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 104, P. 102638 - 102638

Published: Dec. 12, 2024

Language: Английский

Citations

4
Challenges of Investigating Compartmentalized Brain Energy Metabolism Using Nuclear Magnetic Resonance Spectroscopy in vivo DOI Creative Commons
João M. N. Duarte

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 4, 2025

Abstract Brain function requires continuous energy supply. Thus, unraveling brain metabolic regulation is critical not only for our basic understanding of overall function, but also the cellular basis functional neuroimaging techniques. While it known that metabolism exquisitely compartmentalized between astrocytes and neurons, neuro-energetic activity far from fully understood. 1 H nuclear magnetic resonance (NMR) spectroscopy has been widely used to detect variations in metabolite levels, including glutamate GABA, while 13 C NMR employed study compartmentation determine rates coupled activity, focusing mainly on component corresponding excitatory glutamatergic neurotransmission. The oxidative neurons are both associated with rate glutamate-glutamine cycle astrocytes. However, any possible correlation pathways inhibitory GABAergic neurotransmission living remains be experimentally demonstrated. That due low GABA consequent challenge determining a non-invasive manner. This brief review surveys state-of-the-art analyses contributing synthesis using vivo, identifies limitations need overcome future studies.

Language: Английский

Citations

0
Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury DOI
Patricia Cassina, Ernesto Miquel, Laura Martìnez‐Palma

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: 567, P. 227 - 234

Published: Jan. 7, 2025

Language: Английский

Citations

0
SENP1 inhibits aerobic glycolysis in Aβ1-42-incubated astrocytes by promoting PUM2 deSUMOylation DOI Creative Commons
Qianshuo Liu, M. Jiang,

Zening Wang

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 10, 2025

Alzheimer's disease (AD), the most prevalent form of dementia in elderly, involves critical changes such as reduced aerobic glycolysis astrocytes and increased neuronal apoptosis, both which are significant disease's pathology. In our study, treated with amyloid β1-42 (Aβ1-42) to simulate AD conditions exhibited upregulated expressions small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) Pumilio RNA Binding Family Member 2 (PUM2), alongside decreased levels Nuclear factor erythroid 2-related (NRF2). SENP1 is notably SUMOylation enzyme Aβ1-42-exposed astrocytes. Functional assays including Ni2+-Nitrilotriacetic acid (NTA) agarose bead pull-down co-immunoprecipitation (Co-IP) confirmed SENP1's role actively deSUMOylating PUM2, thereby enhancing its stability expression. The interaction between PUM2 3' untranslated region (3'UTR) NRF2 mRNA reduces levels, subsequently diminishing transcriptional activation glycolytic enzymes, Hexokinase (HK1) Glucose Transporter (GLUT1). These contribute observed reduction function astrocytes, exacerbating apoptosis. Targeted interventions, knockdown Senp1 or Pum2 overexpression APPswe/PSEN1dE9 (APP/PS1) transgenic mice, effectively HK1 GLUT1 alleviated cognitive impairment. findings highlight important roles SENP1/PUM2/NRF2 pathway influencing glucose metabolism presenting new potential therapeutic targets for AD. 1. deSUMOylates expression Aβ1-42-microenvironment. 2. binds reducing 3. Reduced promoting effects on 4. decreases leading an increase co-culture apoptosis

Language: Английский

Citations

0
Brain neurons internalise polymeric micron-sized capsules: insights from in vitro and in vivo studies DOI Creative Commons
Olga Kopach, Olga A. Sindeeva, Kaiyu Zheng

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101493 - 101493

Published: Jan. 22, 2025

Nanoengineered encapsulation presents a promising strategy for targeted drug delivery to specific regions in the body. While polyelectrolyte-based biodegradable microcapsules can achieve highly localised release tissues and cell cultures, delivering drugs intracellular sites brain remains significant challenge. In this study, we utilized advanced imaging techniques, both vitro vivo, investigate whether neurons internalise designed delivery. High-resolution live-cell revealed that differentiating N2A cells actively microcapsules, often incorporating multiple capsules per cell. Likewise, primary hippocampal cortical were observed effectively polymeric microcapsules. intact brain, multiplexed two-photon excitation vivo confirmed internalisation of by following somatosensory region. This was time-dependent, correlated with particle size mediated macropinocytosis mechanism appears bypass lysosomal formation. Importantly, presence internalised did not impair neuronal function, as maintained normal firing activity action potential characteristics. Furthermore, no adverse effects after week microcapsule mouse brain. Our findings indicate are effective safe carriers neurons, providing approach therapeutic applications.

Language: Английский

Citations

0
Tailoring the Electrocatalytic Properties of Porphyrin Covalent Organic Frameworks for Highly Selective Oxygen Sensing In Vivo DOI
Jiawei Lai,

Yao Tian,

Huan Wei

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

In vivo selective sensing of oxygen (O2) dynamics in the central nervous system could provide insights into energy metabolism and neural activities. Although electrocatalytic four-electron reduction reaction (ORR) paves an effective way to electrochemical O2 vivo, concurrent hydrogen peroxide (HPRR) within potential windows for ORR unfortunately poses a great challenge conventional mechanism employed sensing. this work, we find that regulation linkers skeleton porphyrin-based covalent organic frameworks (COFs) improve selectivity sensor against (H2O2). The results reveal Co porphyrin active sites facilitate direct pathway COF, enriched with pyrene units, shows enhanced kinetics better tolerance HPRR. theoretical calculation suggests introducing units essentially weakens adsorption H2O2, leading suppression microsensor fabricated COF as electrocatalyst features high real-time monitoring living rat brain.

Language: Английский

Citations

0
Metabolic dysregulation in glaucoma DOI
Xuejiao Yang, Songwei Li, Hao Guo

et al.

Clinical and Experimental Optometry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 7

Published: Feb. 12, 2025

Glaucoma is a multifactorial neurodegenerative disorder characterised by the progressive loss of retinal ganglion cells, ultimately leading to irreversible blindness worldwide. Recent research highlights metabolic dysregulation as crucial factor in pathophysiology glaucoma. This review examines intricate relationship between processes and glaucoma, with focus on key mechanisms such mitochondrial dysfunction, lipid metabolism, glucose roles specific metabolites. Mitochondrial dysfunction commonly observed impaired energy production that compromises cellular viability. Alterations including changes fatty acid profiles peroxidation, contribute injury apoptosis cells. Moreover, disturbances reduced glycolytic activity, affect availability neurotrophic support are vital for cells survival. The also explores metabolites, lactate glutamate, context health, how their may exacerbate glaucomatous damage. Additionally, interplay elevated intraocular pressure analysed, particularly regard its impact ocular blood flow health. Understanding these essential identifying potential therapeutic strategies. By deepening our understanding foundations new avenues effective treatments arise, addressing nature this complex disease improving patient outcomes.

Language: Английский

Citations

0