Synthesis and in vitro evaluation of novel compounds and discovery of a promising iodine-125 radioligand for purinergic P2X7 receptor (P2X7R) DOI Creative Commons

Lin Qiu,

Jinzhi Wang, Manju Tewari

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 118054 - 118054

Published: Dec. 1, 2024

Language: Английский

The neuroinflammatory astrocytic P2X7 receptor: Alzheimer’s disease, ischemic brain injury, and epileptic state DOI Creative Commons
Young Ha Ahn, Yong Tang, Péter Illés

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2023, Volume and Issue: 27(9), P. 763 - 778

Published: Sept. 2, 2023

Introduction Astrocytes have been previously considered as cells supporting neuronal functions, but they are now recognized active players in maintaining central nervous system (CNS) homeostasis. can communicate with other CNS i.e. through the gliotransmitter ATP and P2×7receptors (Rs).

Language: Английский

Citations

11

Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome DOI Creative Commons

Fabrizio Di Giuseppe,

Lucia Ricci‐Vitiani, Roberto Pallini

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 571 - 571

Published: March 25, 2024

Extracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies poor patient prognosis. Given relevance of information provided by cancer cell secretome, we performed a proteomic analysis microvesicles (MVs) exosomes (EXOs) released GBM-derived stem cells (GSCs). The latter, obtained GBM patients, expressed P2X7 receptors (P2X7Rs), positively correlate with growth invasiveness. P2X7R stimulation GSCs caused significant changes EV content, mostly ex novo inducing or upregulating expression proteins related cytoskeleton reorganization, motility/spreading, energy supply, protection against oxidative stress, chromatin remodeling, transcriptional regulation. Most induced/upregulated have already been identified as diagnostic/prognostic factors, while others only reported peripheral tumors. Our findings indicate that enhances transport and, therefore, possible intercellular exchange aggressiveness-increasing GSC-derived EVs. Thus, P2X7Rs could be considered new druggable target human GBM, although these data need confirmed larger experimental sets.

Language: Английский

Citations

4

In memoriam - Francesco di Virgilio: P2X7 receptors in purinergic pathophysiology DOI
Péter Illés, Alexei Verkhratsky, Yong Tang

et al.

Current Opinion in Pharmacology, Journal Year: 2025, Volume and Issue: 80, P. 102503 - 102503

Published: Jan. 23, 2025

Language: Английский

Citations

0

α-Cyanocinnamylboronic acid derivatives are safe, selective anti-inflammatory molecules that inhibit P2X7 receptor function and signaling DOI
Noemi de Jesus Hiller,

Juliana Salles,

Lucas Villas Bôas Hoelz

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117945 - 117945

Published: Feb. 27, 2025

Language: Английский

Citations

0

Advancing Endocrine Disruptors via In Vitro Evaluation: Recognizing the Significance of the Organization for Economic Co-Operation and Development and United States Environmental Protection Agency Guidelines, Embracing New Assessment Methods, and the Urgent Need for a Comprehensive Battery of Tests DOI Creative Commons
Sophie Fouyet,

Marie-Caroline Ferger,

P. Leproux

et al.

Toxics, Journal Year: 2024, Volume and Issue: 12(3), P. 183 - 183

Published: Feb. 28, 2024

Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition their impact on human health environment has stimulated attention research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, industry representatives, collaborating develop robust methodologies guidelines for assessing these disruptors. A key aspect efforts is development standardized testing protocols that aim provide consistent reliable methods identifying characterizing endocrine When evaluating potential activity chemicals, no single test capable detecting all relevant agents. The battery approach designed reduce risk false negative results compounds with toxic potential. weight-of-evidence therefore necessary disruptor evaluation. This considers various types data from multiple sources, overall strength, consistency, reliability evidence. OECD highly regarded scientific rigor, transparency, consensus-based process. It crucial explore new can effectively evaluate risks associated Integrating into a comprehensive framework will enhance assessments facilitate informed decisions regarding regulation management substances, ensuring protection adverse effects.

Language: Английский

Citations

2

A patent review of P2X7 receptor antagonists to treat inflammatory diseases (2018 – present) DOI
Jamshed Iqbal,

Sehrish Bano,

Imtiaz Khan

et al.

Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: 34(4), P. 263 - 271

Published: April 2, 2024

Introduction The purinergic P2×7receptor is expressed on the surface of many different types cells, including immune cells. Targeting P2×7receptors with antagonists has been studied for its potential therapeutic effects in a variety inflammatory illnesses. It plays crucial role control responses.

Language: Английский

Citations

2

Key roles of glial cells in the encephalopathy of prematurity DOI Creative Commons
Juliette Van Steenwinckel, Cindy Bokobza, Mireille Laforge

et al.

Glia, Journal Year: 2023, Volume and Issue: 72(3), P. 475 - 503

Published: Nov. 1, 2023

Abstract Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 gestation. Up to 50% preterm infants develop brain injury, encephalopathy prematurity (EoP), substantially increases their risk for developing lifelong defects motor skills and domains learning, memory, emotional regulation, cognition. We still severely limited our abilities prevent or predict birth. No longer just “support cells,” we now clearly understand during development glia key building healthy brain. Glial dysfunction is hallmark EoP, notably, microgliosis, astrogliosis, oligodendrocyte injury. Our knowledge glial biology exponentially expanding but hasn't developed sufficiently effective neuroregenerative therapies. This review summarizes current state roles with EoP its animal models, description known glial‐cell interactions context such as border‐associated macrophages. The field perinatal medicine relatively small has worked passionately improve understanding etiology coupled detailed mechanistic studies pre‐clinical human cohorts. A primary finding from this collaborations computational biologists, working together complexity subtypes, maturation, impacts short long term will be design therapies outcomes.

Language: Английский

Citations

5

A Species-Specific Anti-Human P2X7 Monoclonal Antibody Reduces Graft-versus-Host Disease in Humanised Mice DOI Creative Commons
Amal Elhage, Peter Cuthbertson, Chloe Sligar

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(9), P. 2263 - 2263

Published: Aug. 31, 2023

Graft-versus-host disease (GVHD) is a T cell-mediated inflammatory disorder that arises from allogeneic haematopoietic stem cell transplantation and often fatal. The P2X7 receptor an extracellular adenosine 5'-triphosphate-gated cation channel expressed on immune cells. Blockade of this with small molecule inhibitors impairs GVHD in humanised mouse model. A species-specific blocking monoclonal antibody (mAb) (clone L4) for human available, affording the opportunity to determine whether donor (human) contributes development mice. Using flow cytometric assays RPMI 8266 murine J774 cells, study confirmed mAb bound impaired P2X7. Furthermore, prevented loss regulatory cells (hTregs) natural killer (hNK) vitro. NOD-scid IL2Rγnull mice were injected 10 × 106 peripheral blood mononuclear (Day 0) anti-hP2X7 or control (100 μg i.p. per mouse, Days 0, 2, 4, 6, 8). increased hTregs hNK at Day 21. Moreover, mAb-treatment reduced clinical histological liver lung compared treatment endpoint. hTregs, hNK, proportions increased, helper 17 decreased These studies indicate blockade (donor) reduces mice, providing first direct evidence role GVHD.

Language: Английский

Citations

4

ATP as a signaling molecule DOI Creative Commons
Babich Lg, Shlykov Sg, Kosterin Sa

et al.

The Ukrainian Biochemical Journal, Journal Year: 2024, Volume and Issue: 96(3), P. 5 - 12

Published: June 14, 2024

The review considers the effects of extracellular ATP mediated by plasma membrane purinoreceptors in cells different tissues, particular, myometrium. Recently published results suggest that cytosolic may also play a role signaling molecule, as indicated detection receptor not only membrane, but mitochondria. authors have shown ionized Ca2+ concentration rat myometrium mitochondria matrix is regulated at absence exogenous Ca2+. concentration-dependent increase [Ca2+]m was affected presence mitochondrial Ca2+-uniporter blocker ruthenium red, pore cyclosporine A, or synthase inhibitor oligomycin. It assumed could be molecule regulates least ions exchange Keywords: exchange, and ATP, mitochondria, P2X7 receptors

Language: Английский

Citations

1

Partners in health and disease: pineal gland and purinergic signalling DOI
Regina P. Markus, Kassiano dos Santos Sousa, Henning Ulrich

et al.

Purinergic Signalling, Journal Year: 2024, Volume and Issue: unknown

Published: July 20, 2024

Language: Английский

Citations

1