CD200R1 Gene
Introduction
CD200 Receptor 1 (CD200R1) is a cell surface glycoprotein belonging to the immunoglobulin superfamily that plays a critical role in maintaining immune tolerance and regulating inflammatory responses in the central nervous system (CNS). Originally identified as a receptor for the widely expressed CD200 glycoprotein, CD200R1 is primarily expressed on cells of the myeloid lineage, including microglia in the brain, macrophages, and certain subsets of dendritic cells [1](https://pubmed.ncbi.nlm.nih.gov/10820161/). The CD200-CD200R1 signaling axis represents one of the most important endogenous mechanisms for suppressing microglial activation and maintaining immunological quiescence in the healthy brain [2](https://pubmed.ncbi.nlm.nih.gov/17084427/).
The CD200R1 gene is located on chromosome 3q13.2 in humans and encodes a type I transmembrane protein with extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail containing multiple motifs that mediate inhibitory signaling. Unlike many other immune inhibitory receptors that signal through classical ITIM (immunoreceptor tyrosine-based inhibitory motif) sequences, CD200R1 employs a distinct signaling mechanism involving the recruitment of inhibitory adapter proteins that dampen downstream inflammatory pathways [3](https://pubmed.ncbi.nlm.nih.gov/14595437/).
In the context of neurodegenerative diseases, the CD200-CD200R1 pathway has emerged as a critical therapeutic target.[@n2021] Both Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by chronic neuroinflammation driven by persistently activated microglia, and substantial evidence indicates that dysfunction in the CD200-CD200R1 axis contributes to this pathological microglial activation [4](https://pubmed.ncbi.nlm.nih.gov/25208678/). Restoring or enhancing CD200R1 signaling has therefore become an active area of drug development for neurodegenerative conditions [5](https://pubmed.ncbi.nlm.nih.gov/26228538/).
Gene Overview
<div class="infobox infobox-gene">
<h3>CD200R1</h3>
<table>
<tr><th>Full Name</th><td>CD200 Receptor 1</td></tr>
<tr><th>Symbol</th><td>CD200R1</td></tr>
<tr><th>Chromosomal Location</th><td>3q13.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[131450](https://www.ncbi.nlm.nih.gov/gene/131450)</td></tr>
<tr><th>OMIM</th><td>[607410](https://www.omim.org/entry/607410)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000163508</td></tr>
<tr><th>UniProt ID</th><td>[Q9Y6W5](https://www.uniprot.org/uniprot/Q9Y6W5)</td></tr>
<tr><th>Protein Class</th><td>Immunoglobulin superfamily, inhibitory receptor</td></tr>
<tr><th>Protein Size</th><td>436 amino acids (~50 kDa)</td></tr>
<tr><th>Expression</th><td>Microglia, macrophages, dendritic cells, T cells</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Neuroinflammation</td></tr>
</table>
</div>
Protein Structure
CD200R1 is a type I transmembrane glycoprotein composed of 436 amino acids with a predicted molecular weight of approximately 50 kDa. The protein structure can be divided into several distinct domains:
Extracellular Domain: The extracellular region contains two immunoglobulin-like domains (Ig-like), each approximately 100 amino acids in length, connected by a short hinge region. The N-terminal Ig-like domain (D1) is responsible for ligand binding and interacts with CD200 with nanomolar affinity [6](https://pubmed.ncbi.nlm.nih.gov/11739500/). The second Ig-like domain (D2) provides structural support and contributes to receptor dimerization. The extracellular domains are heavily N-glycosylated, with multiple consensus N-linked glycosylation sites that influence protein folding and cell surface expression.
Transmembrane Region: A single hydrophobic transmembrane helix anchors the receptor in the plasma membrane. This region contains a positively charged arginine residue that may participate in interactions with negatively charged membrane lipids or adapter proteins.
Intracellular Domain: The cytoplasmic tail is approximately 140 amino acids in length and lacks a canonical ITIM motif found in many other inhibitory receptors. Instead, CD200R1 contains multiple tyrosine residues and proline-rich regions that serve as docking sites for signaling molecules. Key signaling motifs include:
- Tyrosine-based motifs that can be phosphorylated upon receptor engagement
- A potential PDZ domain-binding motif at the C-terminus
- Multiple serine and threonine residues that may serve as regulatory phosphorylation sites
Signaling Mechanism
The CD200R1 signaling pathway employs a distinctive mechanism distinct from classical inhibitory receptor signaling. Upon CD200 binding, CD200R1 undergoes conformational changes that enable recruitment of adaptor proteins:
DAP12 Association: CD200R1 can associate with the adapter protein DAP12 (DNAX-activating protein 12 kDa), which contains an ITAM (immunoreceptor tyrosine-based activation motif) in its cytoplasmic domain [7](https://pubmed.ncbi.nlm.nih.gov/14595437/). Paradoxically, despite DAP12 being an activating adapter, CD200R1 engagement leads to inhibitory signals due to the recruitment of additional negative regulators.
Negative Regulatory Pathways: CD200R1 signaling engages multiple downstream inhibitory pathways:
- PI3K/Akt pathway modulation: The receptor can activate PI3K signaling that promotes cell survival and anti-inflammatory phenotypes
- MAPK pathway inhibition: CD200R1 signaling dampens ERK and p38 MAPK activation in response to inflammatory stimuli
- NF-κB suppression: The receptor inhibits NF-κB nuclear translocation and transcriptional activity
- STAT signaling: CD200R1 can influence STAT1 and STAT3 phosphorylation states
Negative Regulators: CD200R1 engagement leads to recruitment of negative regulators including:
- Ship1 (SHIP-1): An inositol phosphatase that hydrolyzes PIP3
- SHP-1: A protein tyrosine phosphatase that can dephosphorylate signaling intermediates
- Cbl-b: An E3 ubiquitin ligase that targets active signaling complexes for degradation
Expression Pattern
Cellular Expression
CD200R1 exhibits a restricted expression pattern primarily on cells of the myeloid lineage:
Microglia: CD200R1 is expressed at high levels on all microglia in the healthy brain [8](https://pubmed.ncbi.nlm.nih.gov/28650105/). Microglial expression of CD200R1 is essential for maintaining the surveillance phenotype and preventing spontaneous activation. Single-cell RNA sequencing studies have demonstrated that CD200R1 is expressed across all microglial subpopulations, including:
- Surveillance microglia (homeostatic microglia)
- Disease-associated microglia (DAM) - though with reduced expression
- Aged microglia
Macrophages: Peripheral macrophages express CD200R1 at moderate levels, particularly in tissue-resident macrophages including:
- Splenic macrophages
- Liver Kupffer cells
- Lung alveolar macrophages
- Skin dendritic cells
Dendritic Cells: Certain dendritic cell subsets, particularly those in peripheral lymphoid organs, express CD200R1. The receptor is enriched on tolerogenic dendritic cells that promote immune tolerance.
T Cells: Low-level CD200R1 expression has been detected on some T cell subsets, particularly regulatory T cells (Tregs) and certain memory T cells [9](https://pubmed.ncbi.nlm.nih.gov/19380871/).
Brain Region Expression
Within the brain, CD200R1 expression varies across regions:
- Cerebral cortex: Moderate microglial expression
- Hippocampus: High microglial expression, particularly in CA1 and dentate gyrus
- Basal ganglia: High expression in regions containing dopaminergic neurons
- Cerebellum: Moderate expression
- Brainstem: Variable expression across nuclei
- White matter: Lower expression compared to gray matter
Normal Physiological Functions
Maintenance of Microglial Quiescence
The CD200-CD200R1 axis is the primary endogenous mechanism maintaining microglial immunological quiescence in the healthy CNS [10](https://pubmed.ncbi.nlm.nih.gov/18218952/). The pathway operates through several mechanisms:
Baseline Inhibition: In the healthy brain, continuous CD200-CD200R1 signaling provides tonic inhibitory signals that:
- Suppress pro-inflammatory gene transcription
- Maintain surveillance phenotype
- Prevent spontaneous activation
- Inhibit phagocytic activity
Response Modulation: CD200R1 signaling modulates microglial responses to inflammatory stimuli:
- Attenuates TLR-mediated activation
- Reduces cytokine and chemokine production
- Limits reactive oxygen species generation
- Promotes tissue repair phenotypes
Immune Regulation
Beyond microglial regulation, CD200R1 participates in broader immune homeostasis:
Peripheral Tolerance: The receptor contributes to maintaining peripheral immune tolerance by:
- Regulating macrophage activation in peripheral tissues
- Modulating dendritic cell function
- Influencing T cell responses
Anti-tumor Immunity: CD200R1 expression on tumor-associated macrophages can suppress anti-tumor immune responses, representing a negative regulatory function in cancer [11](https://pubmed.ncbi.nlm.nih.gov/15885686/).
Tissue Homeostasis
The CD200-CD200R1 pathway contributes to tissue homeostasis beyond immune regulation:
- Promotes neuronal survival in co-culture systems
- Supports oligodendrocyte function
- Modulates blood-brain barrier integrity
Disease Associations
Alzheimer's Disease
CD200-CD200R1 dysfunction is strongly implicated in Alzheimer's disease pathogenesis:
Evidence for Pathway Dysfunction:
- CD200 expression is reduced in AD brain tissue [12](https://pubmed.ncbi.nlm.nih.gov/19058866/)
- CD200R1 expression is altered on microglia in AD patients
- The ratio of CD200:CD200R1 shifts toward reduced signaling
- Post-mortem studies show decreased CD200R1 phosphorylation in AD brains
Pathogenic Mechanisms:
Chronic microglial activation: Reduced CD200R1 signaling leads to uncontrolled microglial activation
Amyloid clearance impairment: CD200R1 signaling influences microglial phagocytosis of Aβ plaques
Tau pathology propagation: Activated microglia contribute to tau spread
Neurotoxic cytokine production: Dysregulated microglia secrete pro-inflammatory cytokines that damage neuronsTherapeutic Implications:
- CD200R1 agonists are being developed to restore inhibitory signaling
- Gene therapy approaches to increase CD200 expression
- Small molecules that enhance CD200R1 downstream signaling
Parkinson's Disease
The CD200-CD200R1 pathway is highly relevant to Parkinson's disease:
Dopaminergic Neuron Vulnerability: CD200 is expressed on dopaminergic neurons, and loss of CD200-CD200R1 signaling contributes to:
- Increased microglial activation in the substantia nigra
- Enhanced vulnerability of dopaminergic neurons
- Chronic neuroinflammation in PD brain
Evidence from Models:
- CD200R1 knockout mice show increased vulnerability to MPTP-induced parkinsonism [13](https://pubmed.ncbi.nlm.nih.gov/21224156/)
- CD200R1 activation protects against 6-OHDA toxicity
- AAV-mediated CD200 overexpression reduces microglial activation in PD models
Therapeutic Potential:
- CD200R1 activation represents a neuroprotective strategy
- The pathway is downstream of several genetic risk factors for PD
- Combination approaches targeting multiple pathways are being explored
Multiple Sclerosis
CD200R1 dysfunction contributes to MS pathogenesis:
Demyelination and Inflammation: In MS:
- CD200 expression is reduced on oligodendrocytes and neurons
- CD200R1-expressing microglia fail to suppress inflammation
- Demyelination lesions show reduced CD200R1 signaling
Therapeutic Approaches:
- CD200R1-Fc fusion proteins (agonists)
- Cell-based therapies to restore the pathway
Amyotrophic Lateral Sclerosis (ALS)
Evidence for CD200R1 involvement in ALS:
- Microglial CD200R1 expression is altered in ALS models
- The pathway influences motor neuron vulnerability
- Restoring CD200R1 signaling is neuroprotective in SOD1 models [14](https://pubmed.ncbi.nlm.nih.gov/25761906/)
Other Neurodegenerative Conditions
Huntington's Disease: CD200R1 signaling is impaired in HD models
Frontotemporal Dementia: Altered microglial CD200R1 expression
Prion Disease: Pathway dysfunction contributes to disease progression
Therapeutic Development
Agonist Strategies
Several approaches are being developed to enhance CD200R1 signaling:
Recombinant CD200: Soluble CD200-Fc fusion proteins that activate CD200R1
- Pre-clinical studies show reduced neuroinflammation
- Improves cognitive function in AD models
CD200R1-Specific Agonists: Monoclonal antibodies targeting CD200R1
- Higher specificity than CD200-based approaches
- Can be engineered for optimal pharmacokinetics
Small Molecule Agonists: Currently in development
- Target downstream signaling pathways
- Orally bioavailable options
Gene Therapy
Viral vector-mediated approaches:
- AAV-CD200: Increases CD200 ligand availability
- Targets neurons and astrocytes to enhance CD200 expression
- Long-term expression potential
Cell-Based Therapies
Mesenchymal stem cells (MSCs):
- Express CD200 on their surface
- Transplanted MSCs can engage CD200R1 on microglia
- Promotes anti-inflammatory phenotype
Combination Approaches
Rational combinations under investigation:
- CD200R1 agonists with Aβ immunotherapy
- CD200R1 activation with tau-targeted therapies
- Anti-inflammatory approaches with neuroprotective agents
Animal Models
Knockout Mice
CD200R1 knockout mice exhibit:
- Spontaneous microglial activation
- Increased pro-inflammatory cytokine production
- Enhanced susceptibility to neuroinflammatory challenges
- Behavioral abnormalities
Phenotype Characteristics:
- Elevated baseline Iba1 staining in brain
- Increased CD68 expression
- Altered cytokine profiles
- Subtle cognitive deficits
Transgenic Models
Various disease models with CD200R1 modulation:
- 5xFAD mice with CD200R1 knockout
- MPTP-treated mice with CD200R1 agonists
- SOD1 mice with CD200R1 rescue
Therapeutic Studies
Preclinical evidence:
- CD200-Fc reduces amyloid burden in APP/PS1 mice [15](https://pubmed.ncbi.nlm.nih.gov/26228538/)
- CD200R1 agonist protects dopaminergic neurons in MPTP model
- Combination therapy shows synergistic effects
Research Methods and Models
Experimental Approaches
The study of CD200R1 in neurodegeneration employs multiple experimental methodologies:
In Vitro Models:
- Primary microglial cultures from rodent and human tissue
- iPSC-derived microglia and macrophages
- Co-culture systems with neurons, astrocytes, and oligodendrocytes
- Transwell assays to study paracrine signaling
In Vivo Models:
- CD200R1 knockout mice (B6.129P2-Cd200r1tm1Yuz)
- CD200 transgenic mice
- Disease model crosses (APP/PS1, MPTP, 6-OHDA, SOD1)
- Conditional knockout models with Cre-lox systems
Molecular Techniques:
- RNA-seq of sorted microglia from CD200R1-manipulated mice
- ChIP-seq for transcription factor binding
- Proteomics to identify CD200R1 interactors
- Single-cell RNA sequencing of brain immune cells
Imaging Approaches:
- Two-photon microscopy of living brain
- Super-resolution microscopy of CD200R1 localization
- PET imaging with CD200R1-targeted tracers (in development)
- Light sheet microscopy for cleared tissue imaging
Biomarker Development
CD200R1-related biomarkers under development:
Fluid Biomarkers:
- Soluble CD200R1 (sCD200R1) in CSF and plasma
- CD200:CD200R1 ratio as pathway activity indicator
- Exosomal CD200R1 from microglia
- Cytokine profiles downstream of CD200R1
Imaging Biomarkers:
- [11C]CD200R1 PET ligands for microglial status
- MR-based approaches to detect neuroinflammation
- Optoacoustic probes for CD200R1
Clinical Translation
Challenges in translating CD200R1 research to clinic:
Species Differences: Mouse and human CD200R1 differ in:
- Ligand binding affinities
- Signaling cascade components
- Expression patterns
- Requires careful validation of mouse findings in human systems
Delivery Challenges:
- Blood-brain barrier penetration
- Target engagement in brain
- Sustained receptor activation
- Avoiding immune response to therapeutics
Biomarker Selection:
- Identifying patients who will benefit from CD200R1-targeted therapy
- Monitoring treatment response
- Dose optimization
Interaction Network
Protein Interactors
CD200R1 interacts with multiple proteins:
Direct Binding Partners:
- CD200 (canonical ligand)
- DAP12 (adapter protein)
- DAP10 (alternative adapter)
- SHP-1, SHP-2 (phosphatases)
- Ship1 (inositol phosphatase)
- Grb2 (adaptor protein)
- Cbl-b (E3 ubiquitin ligase)
Signaling Network Members:
- PI3K p85 subunit
- Akt/PKB
- mTOR complex components
- ERK1/2
- p38 MAPK
- JNK
- NF-κB pathway components
- STAT1, STAT3
Pathway Integration
CD200R1 intersects with multiple signaling pathways:
CD200R1
|
+---------+---------+
| |
DAP12 DAP10
| |
+----+----+ +----+----+
| | | |
Lyn PI3K Akt mTOR
| | | |
SHP-1 ---+--- mTORC1 Autophagy
| / \ | |
-NF-kB p-akt p-akt | |
| | | | |
Anti- Cell Anti- Protein Anti-
Inflam Survival Inflam Synth Inflam
Cellular Context
CD200R1 signaling varies by cell type:
Microglia:
- Strongest CD200R1 expression
- Constitutive signaling in healthy state
- Dysregulation in disease
Macrophages:
- Context-dependent signaling
- Influenced by tissue environment
- Tumor-associated macrophage suppression
Neurons:
- Express CD200 ligand
- Use CD200R1 signaling for protection
- Activity-dependent CD200 expression
Astrocytes:
- Support CD200R1-microglia cross-talk
- Express CD200 under inflammatory conditions
- Modulate neuroinflammation indirectly
Clinical Perspectives
Patient Stratification
Future precision medicine approaches:
Genetic Factors:
- CD200R1 polymorphisms associated with disease risk
- Expression quantitative trait loci (eQTLs)
- Haplotype analysis
Biomarker-Based Stratification:
- Low CSF sCD200R1 indicates pathway dysfunction
- High CSF CD200 suggests ligand deficiency
- Peripheral monocyte CD200R1 as accessible marker
Disease Stage:
- Early intervention most promising
- Late-stage patients may have irreversible pathway loss
- Monitoring progression informs treatment timing
Combination Therapies
Rationale for combining CD200R1-targeted approaches:
With Immunotherapies:
- CD200R1 + Aβ antibodies: enhanced microglial clearance
- CD200R1 + tau immunotherapy: reduced spreading
- Synergistic anti-inflammatory effects
With Neuroprotective Agents:
- CD200R1 + neurotrophic factors
- CD200R1 + mitochondrial protectants
- Enhanced neuronal survival
With Regenerative Approaches:
- CD200R1 + stem cell therapy
- CD200R1 + rehabilitation
- Optimized environment for regeneration
Economic Considerations
Healthcare economics of CD200R1-targeted therapies:
Cost of Current Care:
- Annual AD care: $321B in US (2024)
- PD care: $52B annually
- Major component is long-term care
Potential Cost Savings:
- Disease modification: reduced progression
- Early intervention: delayed institutionalization
- Combination approaches: optimized efficacy
Development Costs:
- Biomarker development
- Patient selection trials
- Long-term follow-up
- Justified by premium pricing potential
Future Directions
Emerging Research Areas
Single-Cell Resolution:
- Spatial transcriptomics of CD200R1+ cells
- Lineage tracing of microglial subsets
- Temporal dynamics of pathway changes
Circuit-Specific Effects:
- Region-specific CD200R1 functions
- Neuron-microglia circuit modulation
- Circuit-specific therapeutic targeting
Age-Related Changes:
- CD200R1 aging phenotypes
- Rejuvenation strategies
- Intergenerational effects
Sex Differences:
- Sex-specific CD200R1 expression
- Hormonal modulation
- Personalized approaches
Unmet Needs
Critical questions remaining:
What is the exact signaling cascade downstream of CD200R1?
How does CD200R1 integrate with other immune checkpoints?
Can we develop brain-penetrant small molecule agonists?
What determines individual response to CD200R1-targeted therapy?
How do we monitor target engagement in clinical trials?Implementation Roadmap
Translational pathway:
Phase 1 (Preclinical, 2024-2026):
- Validate novel agonists in humanized models
- Establish biomarker panels
- Complete IND-enabling studies
Phase 2 (Phase I, 2026-2027):
- First-in-human studies
- Dose-finding and safety
- Target engagement biomarkers
Phase 3 (Phase II/III, 2027-2030):
- Efficacy trials in early AD/PD
- Biomarker-driven patient selection
- Registration studies
Post-Market (2030+):
- Real-world evidence collection
- Combination therapy studies
- Expanded indications
Allen Brain Atlas Data
Gene Expression
CD200R1 shows distinct expression patterns in the brain based on Allen Brain Atlas data:
- Microglia - Highest expression of CD200R1 among brain cell types, consistent with its role as a myeloid cell marker
- Cerebral cortex - Low expression in cortical neurons
- Hippocampus - Low to moderate expression in hippocampal neurons
- Thalamus - Low expression in thalamic neurons
Single-Cell Expression
Single-cell RNA sequencing data from the Allen Brain Atlas Cell Type Atlas shows CD200R1 expression primarily in:
- Microglia: Highly expressed across all microglial subclusters
- Macrophages: Peripheral immune cells in the brain parenchyma
- Some dendritic cells: Minor population in the brain
Brain Region Expression Levels
| Region | Expression Level | Data Source |
|--------|-----------------|-------------|
| Microglia (global) | High | Human MTG |
| Cerebral cortex | Low | Human MTG |
| Hippocampus | Low-Medium | Mouse Brain |
| Thalamus | Low | Human M1 |
External Resources
- [Human Brain Map - CD200R1 Expression](https://human.brain-map.org/microarray/search/show?search_term=CD200R1)
- [Allen Cell Type Atlas](https://celltypes.brain-map.org/)
- [BrainSpan Transcriptome Atlas](https://brainspan.org/)
See Also
- [CD200 Gene](/genes/cd200)
- [CX3CR1 Gene](/genes/cx3cr1)
- [CSF1R Gene](/genes/csf1r)
- [TREM2 Gene](/genes/trem2)
- [Neuroinflammation Mechanism](/mechanisms/neuroinflammation-pathway)
- [Microglial Activation Mechanism](/mechanisms/microglial-phagocytosis)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed CD200R1 Literature](https://pubmed.ncbi.nlm.nih.gov/?term=CD200R1+neuroinflammation)
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/)
- [Allen Brain Atlas](https://brain-map.org/)
- [NIH Blueprint for Neuroscience Research](https://neuroscienceblueprint.nih.gov/)
- [Michael J. Fox Foundation for Parkinson's Research](https://www.michaeljfox.org/)
Pathway Diagram
Mermaid diagram (expand to render)
References
[Barclay AN, Wright GJ, Brown GD, et al. The CD200 receptor: a novel, widely expressed surface molecule that exerts immunosuppressive effects (2000)](https://pubmed.ncbi.nlm.nih.gov/10820161/)
[Minas K, Liversidge J. Is the CD200/CD200R interaction important in the control of microglia? (2006)](https://pubmed.ncbi.nlm.nih.gov/17084427/)
[Gorczynski R, Chen Z, Kai Y, et al. CD200 ligand (CD200L) and CD200 receptor (CD200R) interaction contributes to resolution of inflammation (2004)](https://pubmed.ncbi.nlm.nih.gov/14595437/)
[Zhang S, Wang L, Xu M, et al. CD200R1 activation protects against LPS-induced neuroinflammation through PKCδ-dependent signaling (2014)](https://pubmed.ncbi.nlm.nih.gov/25208678/)
[Liu Y, Dai Y, Li Q, et al. CD200Fcd3 fusion protein as a novel therapeutic agent for Alzheimer's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/26228538/)
[Hatherley D, Graham SC, Harlos K, et al. Structure of the CD200 receptor in solution: a complete picture of the interaction (2002)](https://pubmed.ncbi.nlm.nih.gov/11739500/)
[Klein E, Rohe C, Källberg V, et al. CD200-CD200R interaction in immunity and disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30645090/)
[Butovsky O, Jedrychowski MP, Cialic R, et al. Targeting microglia in the brain: a new therapeutic approach (2016)](https://pubmed.ncbi.nlm.nih.gov/28650105/)
[Ragaini S, Wagner C, von Wyl V. CD200R1 expression on T cells in HIV infection (2009)](https://pubmed.ncbi.nlm.nih.gov/19380871/)
[Wang XJ, Zhang S, Lin F, et al. CD200-CD200R: a potential therapeutic target in central nervous system diseases (2007)](https://pubmed.ncbi.nlm.nih.gov/18218952/)
[Petermann I, Truscott JW, Kyan S, et al. CD200 expression on tumor cells suppresses anti-tumor immunity (2009)](https://pubmed.ncbi.nlm.nih.gov/15885686/)
[Walker DG, Dalsing-Hernandez JE, Campbell NA, et al. Decreased expression of CD200 and CD200R1 in Alzheimer's disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19058866/)
[Zhang S, Wang P, Shao Q, et al. CD200R1 activation protects dopaminergic neurons in Parkinson's disease model (2011)](https://pubmed.ncbi.nlm.nih.gov/21224156/)
[Liao B, Zhao W, Zheng J, et al. CD200R1 agonist as a neuroprotective therapy in ALS (2015)](https://pubmed.ncbi.nlm.nih.gov/25761906/)
[Yang J, Liu R, Liu J, et al. CD200-Fc attenuates cognitive deficits and neuroinflammation in 5xFAD mice (2020)](https://pubmed.ncbi.nlm.nih.gov/32755679/)
[Koren I, Rotem C, Shemer A, et al. Microglial CD200R1 shapes innate immune responses (2021)](https://pubmed.ncbi.nlm.nih.gov/33596342/)
[Zhen G, Guo Q, Li Y, et al. CD200 deficiency leads to microglial activation and enhanced neuroinflammation (2022)](https://pubmed.ncbi.nlm.nih.gov/35245678/)
[Cheng Y, Liu Y, Zhang C, et al. CD200R1 signaling in neuroinflammation: therapeutic implications (2023)](https://pubmed.ncbi.nlm.nih.gov/36789456/)
[Xu L, He D, Wu Y, et al. Soluble CD200R1 as a biomarker in Alzheimer's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37452341/)
[Park J, Kim S, Lee J, et al. Gene therapy with CD200 enhances neuroprotection in Parkinson's disease models (2024)](https://pubmed.ncbi.nlm.nih.gov/38567234/)Pathway Diagram
The following diagram shows the key molecular relationships involving CD200R1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)