Purinergic P2Y12 Inverse Agonist Therapy
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Hypotheses from Same Analysis (6)
These hypotheses emerged from the same multi-agent debate that produced this hypothesis.
Description
Molecular Mechanism and Rationale
The P2Y12 receptor, encoded by the P2RY12 gene, represents a critical component of microglial surveillance and activation machinery in the central nervous system. This Gi/Go-coupled purinergic receptor responds to extracellular adenosine diphosphate (ADP) and adenosine triphosphate (ATP) released from neurons and other glial cells. Under physiological conditions, P2Y12 receptors maintain microglial processes in a dynamic, highly motile state that enables continuous surveillance of the synaptic environment. However, in neurodegenerative conditions, chronic activation of this pathway leads to excessive microglial process extension and inappropriate synaptic pruning that contributes to neuronal network dysfunction.
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3D Protein Structure
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Dimension Scores
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✓ Supporting Evidence 17
P2Y12 receptor mediates microglial process extension toward sites of neuronal injury; sustained activation dri… HIGH▼
CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.
P2Y12 expression is a homeostatic microglial marker lost in disease-associated microglia (DAM); therapeutic mo… HIGH▼
Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)-/- Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. VIDEO ABSTRACT.
P2Y12 receptor signaling on microglia contributes to tau pathology progression through complement-dependent sy… HIGH▼
P2Y12 inverse agonism (vs simple antagonism) could constitutively suppress basal microglial surveillance signa… MODERATE▼
BACKGROUND: The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed. METHODS: A unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood. RESULTS: Here, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR
Platelet P2Y12 inhibitors (ticagrelor, prasugrel) have established safety profiles; CNS-penetrant variants cou… MODERATE▼
ADP-P2Y12 signaling axis amplifies NLRP3 inflammasome activation in microglia; P2Y12 blockade reduces IL-1β re… HIGH▼
The developmental journey of cortical interneurons encounters several activity-dependent milestones. During the early postnatal period in developing mice, GABAergic neurons are transient preferential recipients of thalamic inputs and undergo activity-dependent migration arrest, wiring, and programmed cell-death. Despite their importance for the emergence of sensory experience and the role of activity in their integration into cortical networks, the collective dynamics of GABAergic neurons during that neonatal period remain unknown. Here, we study coordinated activity in GABAergic cells of the mouse barrel cortex using in vivo calcium imaging. We uncover a transient structure in GABAergic population dynamics that disappears in a sensory-dependent process. Its building blocks are anatomically clustered GABAergic assemblies mostly composed by prospective parvalbumin-expressing cells. These progressively widen their territories until forming a uniform perisomatic GABAergic network. Such transient patterning of GABAergic activity is a functional scaffold that links the cortex to the external world prior to active exploration. VIDEO ABSTRACT.
Single-nucleus RNA-seq identifies P2Y12-high microglial cluster enriched around amyloid plaques with pro-phago… HIGH▼
Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes across 16 cancer types, uncovering previously undescribed T cell states and heterogeneous subpopulations of follicular helper, regulatory and proliferative T cells. We identified a unique stress response state, TSTR, characterized by heat shock gene expression. TSTR cells are detectable in situ in the tumor microenvironment across various cancer types, mostly within lymphocyte aggregates or potential tertiary lymphoid structures in tumor beds or surrounding tumor edges. T cell states/compositions correlated with genomic, pathological and clinical features in 375 patients from 23 cohorts, including 171 patients who received immune checkpoint blockade therapy. We also found significantly upregulated heat shock gene expression in intratumoral CD4/CD8+ cells following immune checkpoint blockade treatment, particularly in nonresponsive tumors, suggesting a potential role of TSTR cells in immunotherapy resistance. Our well-annotated T cell reference maps, web portal and automatic alignment/annotation tool could provide valuable resources for T cell therapy optimization and biomarker discovery.
The Dual Role of P2RY12: Impact of Polymorphism and Expression on Ischemic Events and Bleeding in Patients wit… MEDIUM▼
BACKGROUND: For patients with ST-segment elevation myocardial infarction (STEMI) on antiplatelet therapy, how P2RY12 single nucleotide polymorphisms (SNPs) and expression influence the ischemia-bleeding balance remains poorly defined. METHODS: This prospective cohort study enrolled patients with STEMI who underwent percutaneous coronary intervention and received ticagrelor therapy between 2018 and 2020. The main outcomes were major adverse cardiovascular events (MACE) and bleeding (Bleeding Academic Research Consortium grade ≥2) within two years. A Cox model was used to examine the effects of P2RY12 SNPs on both events. Additionally, the P2RY12 genetic expression scores were constructed to further evaluate the association between its expression levels and both events. RESULTS: A total of 1,828 STEMI patients were included, with 194 MACE (10.61%) and 237 bleeding events (12.96%) recorded. Compared with the rs10755105 C/C, the MACE hazard ratios (HRs) (95% CI) of T/C and T/T carriers were 0.57 (0.42-0.79) and 0.67 (0.45-1.00), respectively, while the HRs (95% CI) for bleeding were 1.35 (0.99-1.85) and 1.53 (1.06-2.20), respectively. P2RY12 expression scores showed a U-shaped relationship with MACE risk and an inverse U-shaped association with bleeding (Pnonlinear < 0.05). Compared with the medium expression group, the HRs (95% CI) for MACE in the low and high groups were 1.84 (1.28-2.66) and 1.40 (0.83-2.34), respectively, and the corresponding values for bleeding were 0.77 (0.
Clopidogrel Administration Impairs Neurovascular Unit Recovery and Exacerbates Amyloid Beta Accumulation in Ag… MEDIUM▼
Clopidogrel has been the most commonly used therapy for preventing secondary cardiovascular events since 1997 by inhibiting the purinergic receptor P2Y, G-protein coupled, 12 protein receptor (P2RY12). P2RY12 is critical for microglia function in the brain, where it facilitates repair processes following injury. Under normal conditions, the blood-brain barrier (BBB) prevents peripheral drugs like clopidogrel from entering the brain. However, stroke-induced BBB disruption may allow clopidogrel to interfere with neural recovery by impairing microglia activity. Recently, we demonstrated that clopidogrel worsened cognitive outcomes in young mice after stroke. In this study, we examined the effects of clopidogrel on aged mice, focusing on survival, body weight, neurovascular changes, immune response, and amyloid beta accumulation. Aged male mice underwent photothrombotic stroke (or sham surgery) and received daily clopidogrel or control treatment for 14 days. On day 15, brain tissue was analyzed. Clopidogrel treatment significantly reduced survival and body weight, decreased vessel density, increased vascular permeability, altered microglia activity, and increased amyloid beta levels in the peri-infarct region. Notably, some of these effects were not observed in young mice. These results suggest that BBB disruption in stroke mice enables clopidogrel to enter the central nervous system, where it impairs microglia-mediated restoration of BBB integrity and promotes amyloid accumulati
P2 purinergic receptors in systemic lupus erythematosus: from experimental findings to therapeutic perspective… MEDIUM▼
P2 purinergic receptors are activated by extracellular adenosine triphosphate and other nucleotides released during inflammatory processes, cellular stress responses, and amplification by NETosis, thereby serving as pivotal mediators of both innate and adaptive immunity. In patients with active systemic lupus erythematosus (SLE), emerging evidence highlights the critical roles of distinct P2 receptors: P2RX4 and P2RY11 in initiating the immune response; P2RY2 in orchestrating immune cell recruitment; P2RX7 in promoting pro-inflammatory states coupled with impaired regulatory mechanisms; and P2RY12 as a driver of type I interferon signaling. Therapeutic targeting of these receptors through selective antagonists has demonstrated efficacy in preclinical lupus-prone models to restore regulatory functions (P2RX7), to control inflammation (P2RX7), type I interferon pathway (P2RY12), autoantibody production (P2RX4 and P2RX7), and glomerulonephritis (P2RX4, P2RX7, P2RY2, and P2RY12). In SLE, selective P2 antagonists are under investigation with major challenges regarding cellular specificity, therapeutic efficacy, and side effects.
[Advantageous therapeutic pathways and mechanisms of Jianpi Huogu Formula in treating steroid-induced osteonec… MEDIUM▼
Based on integrated analysis of multi-source heterogeneous biomedical data combined with animal experimental validation, this study systematically explored the advantageous therapeutic pathways and molecular mechanisms of Jianpi Huogu Formula(JPHGF) in treating steroid-induced osteonecrosis of the femoral head(SONFH). First, the candidate active components and targets of JPHGF were obtained from the Encyclopedia of Traditional Chinese Medicine(ETCM v 2.0). Meanwhile, the Human Phenotype Ontology(HPO) database was used to identify potential genes associated with the corresponding syndrome pattern. Finally, clinical transcriptomic data were analyzed to obtain relevant targets for the phlegm-blood stasis blocking collateral syndrome of SONFH. The intersection of these three types of targets was used to construct a multidimensional "drug-ingredient-disease-syndrome" network. The STRING database was employed for protein-protein interaction(PPI) network analysis, and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of core targets was performed via the DAVID platform to predict key biological processes and signaling pathways. Pharmacodynamic and mechanistic validation was subsequently conducted using a rat model of SONFH with phlegm-blood stasis obstructing collateral syndrome. Data integration and mining yielded a "disease and syndrome gene-formula and drug target" network containing 146 core targets. Pathway enrichment analysis ind
BACKGROUND: To evaluate the association of the purinergic receptor P2Y, G-protein coupled, 12 (P2Y12) gene polymorphisms with susceptibility to different etiological stroke subtypes. METHODS: A total of 459 first-ever acute ischemic stroke patients were classified into large-artery atherosclerosis (LAA, n = 163), small-vessel occlusion (SVO, n = 204), and cardioembolism (CE, n = 92) based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Direct sequencing was used to screen these three stroke subtypes and non-stroke controls for P2Y12 polymorphisms: a T→C transition at 744 nucleotides (nt) downstream of intron 5's start site (i-T744C) and a C→T transition at 34 nt downstream of exon 2's start site (C34T). Based on the results of multivariate logistic analyses, a prediction model was established via a nomogram that incorporated genomic and clinical variables to quantify the risk of LAA stroke. RESULTS: Significant differences in the P2Y12 i-T744C genotype and allele frequencies were observed between LAA patients and controls. After adjusting for confounding factors, the dominant model (p = 0.009) and additive model (p = 0.023) revealed that the i-T744C polymorphism was significantly associated with increased susceptibility to LAA. No significant associations were found for the SVO and CE stroke subtypes. Moreover, the C34T polymorphism was not an independent factor for any stroke subtype. We further constructed a nomogram prediction model for LAA stroke bas
Paper demonstrates microglial P2RY12's role in microvasculature protection, aligning with the hypothesis's foc…▼
Paper investigates sex-specific microglial neuronal pruning mechanisms, consistent with the hypothesis's explo…▼
Paper examines microglia's role in modulating cortical information processing, which directly relates to the h…▼
Paper highlights microglial activation's role in neurodegeneration, supporting the hypothesis's premise of tar…▼
✗ Opposing Evidence 7
P2Y12 is also expressed on platelets; CNS-targeted delivery is essential to avoid bleeding complications from … HIGH▼
P2Y12 signaling is required for microglial barrier formation around amyloid plaques; complete inhibition could… HIGH▼
Inverse agonists are pharmacologically more complex than antagonists; achieving brain-penetrant inverse agonis… MODERATE▼
BACKGROUND: The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed. METHODS: A unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood. RESULTS: Here, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR
Microglial P2Y12 expression decreases naturally in advanced AD; therapeutic inhibition may have limited benefi… MODERATE▼
Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)-/- Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. VIDEO ABSTRACT.
Epidemiological studies of clopidogrel users show no clear AD risk reduction, though brain penetrance of exist… LOW▼
Immune checkpoint blockade has demonstrated remarkable efficacy in hepatocellular carcinoma (HCC) but is also commonly accompanied by immune-related adverse events (irAEs). However, the association between irAEs and antitumor efficacy in HCC patients remains unknown. All patients with HCC treated with anti-PD-1 antibodies from July 2018 to November 2019 were analyzed and divided into different groups according to their irAEs' status. In total, 101 HCC patients, including 21 (20.8%) patients who presented with irAEs (irAEs+ ), were enrolled. Among the adverse events, rash (n = 9, 8.9%) was the most frequent irAE, followed by mucositis (n = 3, 3.0%) and thyroiditis (n = 3, 3.0%). Patients in the irAEs+ group showed a higher tumor response rate than those in the irAEs- group (overall response rate: 28.6% vs 6.3%, P = .011; disease control rate: 85.7% vs 60.0%, P = .028). The median progression-free survival (PFS) times were 14.8 months in the irAEs+ group and 4.1 months in the irAEs- group (P < .001). Further analysis based on the presence or absence of rash showed that the PFS of the patients in the irAEs+ /rash+ group was better than that of those in the irAEs+ /rash- or irAEs- group (all P < .05). Multivariate analysis showed that irAEs were an independent prognostic factor for PFS (hazard ratio [HR]: 0.22, P = .002). Thus, the occurrence of irAEs, especially rash, was associated with markedly improved PFS. Awareness of irAEs may help classify the subtype of HCC patients with
Thienopyridines have a well-established role in the treatment of coronary artery disease, especially in the setting of acute coronary syndromes and percutaneous coronary interventions. Ticlopidine, the first FDA-approved thienopyridine, was shown to be effective in reducing coronary events in high risk patients, but the original enthusiasm was hampered by concerns about its serious bone marrow toxicity. Clopidogrel a second generation thienopyridine with lesser side effects, is not only at least
Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogr… MEDIUM▼
Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y(12) receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel. Joint Utilization of Medica
🧬 Theorist Proposes novel mechanisms and generates creative hypotheses ▼
Novel Therapeutic Hypotheses for Synaptic Pruning in Early Alzheimer's Disease
Hypothesis 1: Complement C1q Mimetic Decoy Therapy
Description: Engineer synthetic C1q mimetics that bind to synaptic "eat-me" signals without activating downstream complement cascade, effectively saturating microglial recognition sites and preventing pathological synaptic elimination. These decoys would competitively inhibit authentic C1q binding while lacking the Fc-like domain necessary for microglial phagocytosis activation.Target: C1Q complement component subunit A (C1QA) and microglial compleme
🔍 Skeptic Identifies weaknesses, alternative explanations, and methodological concerns ▼
Critical Evaluation of Synaptic Pruning Therapeutic Hypotheses
Hypothesis 1: Complement C1q Mimetic Decoy Therapy
Specific Weaknesses:
- Selectivity Problem: C1q has essential physiological roles beyond synaptic pruning, including pathogen clearance and apoptotic cell removal. Broad C1q inhibition could compromise immune function and debris clearance.
- Dosing Paradox: The therapeutic window may be extremely narrow - insufficient decoy concentration won't compete effectively, while excess may trigger non-specific immune responses.
- Structural Complexity: C1q is a massiv
🎯 Domain Expert Assesses practical feasibility, druggability, and clinical translation ▼
Practical Feasibility Assessment: Synaptic Pruning Therapeutics
Hypothesis 1: Complement C1q Mimetic Decoy Therapy
Revised Confidence: 0.45Druggability Assessment
Target Class: Protein-protein interaction (PPI) - historically challenging but increasingly tractable Chemical Matter:- Large molecule approach: Engineered proteins/peptides mimicking C1q globular heads (22 kDa each)
- Small molecule approach: PPI inhibitors targeting C1q-CR3 interface (challenging given large interaction surface ~1,500 Ų)
- Best bet: Antibody-based decoys or engineered protein f
⚖ Synthesizer Integrates perspectives and produces final ranked assessments ▼
Price History
| Event | Price | Change | Source | Time | |
|---|---|---|---|---|---|
| 📄 | New Evidence | $0.505 | ▲ 1.5% | evidence_batch_update | 2026-04-13 02:18 |
| 📄 | New Evidence | $0.498 | ▲ 3.7% | evidence_batch_update | 2026-04-13 02:18 |
| ⚖ | Recalibrated | $0.480 | ▼ 1.9% | 2026-04-12 05:13 | |
| ⚖ | Recalibrated | $0.489 | ▼ 1.1% | 2026-04-10 15:58 | |
| ⚖ | Recalibrated | $0.495 | ▲ 1.4% | 2026-04-10 15:53 | |
| ⚖ | Recalibrated | $0.488 | ▼ 2.0% | 2026-04-08 18:39 | |
| ⚖ | Recalibrated | $0.498 | ▼ 0.4% | 2026-04-06 04:04 | |
| ⚖ | Recalibrated | $0.500 | ▼ 0.7% | 2026-04-04 16:38 | |
| ⚖ | Recalibrated | $0.504 | ▼ 1.5% | 2026-04-04 16:02 | |
| 📄 | New Evidence | $0.511 | ▲ 1.8% | evidence_batch_update | 2026-04-04 09:08 |
| ⚖ | Recalibrated | $0.502 | ▼ 30.5% | 2026-04-03 23:46 | |
| 📄 | New Evidence | $0.722 | ▲ 0.8% | evidence_batch_update | 2026-04-03 01:06 |
| ⚖ | Recalibrated | $0.716 | ▲ 5.8% | market_dynamics | 2026-04-03 01:06 |
| 📄 | New Evidence | $0.677 | ▲ 2.1% | evidence_batch_update | 2026-04-03 01:06 |
| ⚖ | Recalibrated | $0.664 | ▲ 24.6% | market_dynamics | 2026-04-03 01:06 |
Clinical Trials (10) Relevance: 62%
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📚 Cited Papers (37)
📓 Linked Notebooks (1)
Wiki Pages
KG Entities (34)
Dependency Graph (4 upstream, 1 downstream)
Linked Experiments (6)
Related Hypotheses
Estimated Development
🧪 Falsifiable Predictions (5)
Knowledge Subgraph (75 edges)
contributes to (1)
fuels (1)
implicated in (7)
maintains (1)
participates in (4)
rate limits (1)
suppresses (1)
Mechanism Pathway for P2RY12
Molecular pathway showing key causal relationships underlying this hypothesis
graph TD
P2RY12["P2RY12"] -->|regulates| microglial_process_motili["microglial_process_motility"]
HK2["HK2"] -->|co discussed| P2RY12_1["P2RY12"]
TREM2["TREM2"] -->|co discussed| P2RY12_2["P2RY12"]
P2RY12_3["P2RY12"] -->|co discussed| C1Q["C1Q"]
P2RY12_4["P2RY12"] -->|co discussed| CX3CR1["CX3CR1"]
P2RY12_5["P2RY12"] -->|co discussed| ANXA1["ANXA1"]
CX3CR1_6["CX3CR1"] -->|co discussed| P2RY12_7["P2RY12"]
P2RY12_8["P2RY12"] -->|co discussed| HK2_9["HK2"]
ANXA1_10["ANXA1"] -->|co discussed| P2RY12_11["P2RY12"]
ANXA1_12["ANXA1"] -->|co associated with| P2RY12_13["P2RY12"]
CX3CR1_14["CX3CR1"] -->|co associated with| P2RY12_15["P2RY12"]
HK2_16["HK2"] -->|co associated with| P2RY12_17["P2RY12"]
P2RY12_18["P2RY12"] -->|co associated with| TREM2_19["TREM2"]
style P2RY12 fill:#ce93d8,stroke:#333,color:#000
style microglial_process_motili fill:#4fc3f7,stroke:#333,color:#000
style HK2 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_1 fill:#ce93d8,stroke:#333,color:#000
style TREM2 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_2 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_3 fill:#ce93d8,stroke:#333,color:#000
style C1Q fill:#ce93d8,stroke:#333,color:#000
style P2RY12_4 fill:#ce93d8,stroke:#333,color:#000
style CX3CR1 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_5 fill:#ce93d8,stroke:#333,color:#000
style ANXA1 fill:#ce93d8,stroke:#333,color:#000
style CX3CR1_6 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_7 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_8 fill:#ce93d8,stroke:#333,color:#000
style HK2_9 fill:#ce93d8,stroke:#333,color:#000
style ANXA1_10 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_11 fill:#ce93d8,stroke:#333,color:#000
style ANXA1_12 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_13 fill:#ce93d8,stroke:#333,color:#000
style CX3CR1_14 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_15 fill:#ce93d8,stroke:#333,color:#000
style HK2_16 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_17 fill:#ce93d8,stroke:#333,color:#000
style P2RY12_18 fill:#ce93d8,stroke:#333,color:#000
style TREM2_19 fill:#ce93d8,stroke:#333,color:#000
3D Protein Structure
🧬 P2RY12 — PDB 4NTJ Click to expand 3D viewer
Source Analysis
Synaptic pruning by microglia in early AD
neurodegeneration | 2026-04-01 | completed