Open research questions in Adenosine and Purinergic Signaling
163 gap statements mined from Adenosine and Purinergic Signaling papers in our 7.9M-paper local library, which holds 811 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The lack of understanding of YqeK's physiological role in S. aureus. The need to characterize the transcriptional profile of the yqeK mutant. The importance of determining YqeK's impact on stress adaptation and virulence gene expression.
Loss of the Ap 4 A hydrolase YqeK impairs stress adaptation and virulence gene expression in Staphylococcus aureus · 2026 · DOIThe lack of selectivity of natural polyphenols and experimental inhibitors. The need for isoform- and cell-specific modulators. The limited understanding of the interactions between natural polyphenols and purinergic receptors.
The role of natural polyphenols in purinergic signaling: from molecular mechanisms to physiological implications · 2026 · DOIThe study addresses the need to investigate the contribution of P2Y6 to ARDS. The researchers seek to define the role of P2Y6 in global P2ry6-deficient mice and conditional knockout models.
Cell-type-specific regulation of acute respiratory distress syndrome by P2RY6-expressing CD11c+ cells · 2026 · DOIThe need for more research on the therapeutic potential of pannexins in cardiac dysfunction. The challenge of translating findings from animal models to human disease.
Most studies have been carried out on the WT fully functional receptor variant. The role of P2X7 variants in different processes and diseases is not fully understood. There is a need for further investigation of the function of human P2X7 splice variants and polymorphisms.
It highlights the need for further research on the therapeutic potential of adenosine receptors.
Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases · 2024 · DOIThe mechanisms by which the P2X7 receptor promotes antigen cross-dressing in DCs are unknown. The role of the P2X7 receptor in macrophages and its effect on antigen presentation is not fully understood.
P2X7 Receptor in Dendritic Cells and Macrophages: Implications in Antigen Presentation and T Lymphocyte Activation · 2024 · DOIThe lack of understanding of the role of the P2X7 receptor in chronic inflammation and carcinogenic changes in the intestine. The need to investigate the signaling pathways and immune responses triggered by P2X7R activation. The requirement to identify novel therapeutic targets for inflammatory bowel disease and colorectal cancer.
Persistent Activation of the P2X7 Receptor Underlies Chronic Inflammation and Carcinogenic Changes in the Intestine · 2024 · DOIFurther research on mechanistic actions and clinical efficacy is necessary to validate their therapeutic potential and develop effective phytotherapeutics.
P2X7 Receptor Modulators from Natural Products: Their Actions on Inflammatory and Painful Chronic Diseases · 2026 · DOIWhether dual targeting of KRAS-MAPK and CD73 signaling creates a therapeutic opportunity to improve tumor control remains unexplored.
Oncogenic KRAS-MAPK signaling sustains a CD73 dependent therapeutic vulnerability in pancreatic cancer · 2026 · DOIExtracellular ATP is rapidly released after tissue injury, but how ATP-derived signals support regenerative repair remains incompletely understood.
P2RY11–SIRT1–PGC-1α–dependent mitochondrial redox and bioenergetic regulation of macrophages drives fin regeneration in zebrafish · 2026 · DOIThe role of adenosine receptor 3 (AR3) signaling in adipogenesis remains unclear.
Adenosine Receptor 3 Antagonism Suppresses Adipogenesis via the EREG ‐ EGFR ‐Leptin Axis in Multipotent Cells · 2026 · DOIExercise training can attenuate hypertension-related disturbances in purinergic pathways, but its effects on renal purine metabolism and purinergic receptor expression remain poorly understood.
Exercise attenuates hypertension-induced renal dysfunction alongside changes in purine metabolism and A2A and P2X7 receptor expression · 2026 · DOIWhile previous studies have investigated the expression of ENT1 in fetal and neonatal brains, its neuroanatomical distribution in adult and aged mouse brains has not been fully elucidated.
The expression profile of type 1 equilibrative nucleoside transporter in aged C57BL/6J mouse brain · 2025 · DOIHowever, the role of TGF-β1 in regulating of pannexin1 channels and cell apoptosis remains unclear.
Third, regarding the cell specificity of ADA function, although single-cell analysis revealed high expression of ADA in plasma cells and pDCs, the exact functional consequences in these specific immune cell subsets remain to be explored.
Exploring the role of adenosine deaminase in esophageal cancer and its potential for traditional Chinese medicine intervention · 2026 · DOIHowever, what these signals are and how Ca2+ signaling cascades influence transcriptional programs remains unclear. Ca2+ transients have also been implicated in oncogenesis, including gliomagenesis, although the mechanisms of their generation and their effectors remain incompletely characterized.
Future studies are needed to directly measure the spatiotemporal dynamics of UDP in the SCG post-ischemia and to identify the specific cell types responsible for its release, in order to precisely elucidate its origin.
P2Y6 receptor in the superior cervical ganglion: a key mediator of post-myocardial ischemic sympathetic hyperexcitability via NF-κB mediated neuroinflammation · 2026 · DOIMoreover, our results suggest that the ion selectivity of P2X receptors may arise from the coordinated contributions of multiple distributed structural elements, whose individual mechanisms and relative contributions to ion selectivity remain to be elucidated.
Natural polyphenols and experimental inhibitors do not distinguish between P2X7A and P2X7B, nor among P2X receptor subtypes, - This lack of selectivity limits translational application, as non-specific targeting may suppress beneficial immune responses while failing to inhibit tumour-promoting…
The role of natural polyphenols in purinergic signaling: from molecular mechanisms to physiological implications · 2026 · DOIThe lack of knowledge of key underlying mechanisms has limited the development of effective therapeutics, - Research exploring Panx1 function in non-ischemic heart disease is currently in its infancy, - Evidence for Panx1 signaling in non-ischemic heart disease is male-dominant, - The use case of spironolactone in heart failure with preserved ejection fraction (HFpEF) is less…
The contradiction between epidemiological and animal research needs to be investigated further to check the effects of caffeine on HD, - Results must be confirmed by other research, including studies with bigger HD sample populations and longer monitoring times, - An epidemiological study is required to conclude the long-term impact of caffeine usage on the onset and/or progression…
Caffeine: A Multifunctional Efficacious Molecule with Diverse Health Implications and Emerging Delivery Systems · 2024 · DOIFurther research utilizing animal models is necessary to fully understand the mechanisms that link caffeine to MJD, - Other research, including studies with bigger HD sample populations and longer monitoring times, is needed to confirm the correlation between caffeine intake and HD, - More studies are needed to confirm the correlation between caffeine intake…
Caffeine: A Multifunctional Efficacious Molecule with Diverse Health Implications and Emerging Delivery Systems · 2024 · DOIInvestigating the role of P2X7 variants in different processes and diseases, - Studying the expression of P2X7 SNPs in human diseases, - Examining the potential of P2X7-targeting antibodies as a new anticancer…
Investigating the exact mechanism of P2X7R in antigen presentation, - Studying the role of P2X7R in different types of immune cells, - Exploring the potential of P2X7R as a target for immunological…
P2X7 Receptor in Dendritic Cells and Macrophages: Implications in Antigen Presentation and T Lymphocyte Activation · 2024 · DOI
Most-cited papers in Adenosine and Purinergic Signaling
- Inositol trisphosphate, a novel second messenger in cellular signal transduction · Nature · 1984 · 4,728 citations
- Inositol phosphates and cell signalling · Nature · 1989 · 3,159 citations
- Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line · Science · 1992 · 2,361 citations
- A Molecular and Cellular Theory of Depression · Archives of General Psychiatry · 1997 · 1,699 citations
- ADENOSINE-DEAMINASE DEFICIENCY IN TWO PATIENTS WITH SEVERELY IMPAIRED CELLULAR IMMUNITY · The Lancet · 1972 · 1,193 citations
- From purines to purinergic signalling: molecular functions and human diseases · Signal Transduction and Targeted Therapy · 2021 · 462 citations
- Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity · Nature Cancer · 2020 · 349 citations
- Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis · Cancer Discovery · 2020 · 294 citations
- Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease · Nature Medicine · 2021 · 281 citations
- ATP and cancer immunosurveillance · The EMBO Journal · 2021 · 229 citations
Most recent work
- Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial · Nature Medicine · 2026
- ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer · Gastroenterology · 2026
- CD39/CD73-mediated immunosuppression and tumor aggressiveness in bladder cancer · Cancer Immunology Immunotherapy · 2026
- Activated CD38+ mast cells promote gastric cancer progression by suppressing CD8+ T cell cytotoxic activity through adenosine metabolism · Cell Reports · 2026
- CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation · Journal for ImmunoTherapy of Cancer · 2026
- Methodological guidelines for P2X receptor assays and data interpretation · Cell Death and Disease · 2026
- Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions · Inflammation · 2026
- Regulatory T-cell Sensing of Extracellular ATP via P2RX7 Promotes Their Accumulation and Suppression and Drives Lung Tumor Growth · Cancer Immunology Research · 2026
- Reprogramming lysosomal–purinergic crosstalk governs the synergistic attenuation of NLRP3 inflammasome activation by cyclodextrin–P2X7 blockade in diabetic rats · European Journal of Pharmacology · 2026
- P2X7 receptors as targets for neuroprotection · Neuropharmacology · 2026
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