mechanism 1,906 words KG: ent-gene-28e2cb01 2026-03-24
evidence:strongmechanismmechanismspublished
Contents

Cholecalciferol (Vitamin D3) as TREM2 Agonist

🔬 Protein Info
Gene Symbolent-gene-28e2cb01
Transmembrane helixSingle pass through the membrane
Cytoplasmic tailShort tail lacking intrinsic signaling capacity
Cholecalciferol (D3)Synthesized in skin upon UVB exposure, also obtained from diet
Ergocalciferol (D2)Obtained from plant sources
25-hydroxyvitamin D [25(OH)D]Major circulating form, measured in clinical assays
1,25-dihydroxyvitamin D [1,25(OH)2D]Active hormone form
Vitamin D receptor (VDR)Nuclear receptor in neurons, astrocytes, and microglia
CYP27B11-alpha hydroxylase for local activation
CYP24A1Catabolic enzyme regulating vitamin D levels
Binding affinityKd approximately 100 nM as measured by surface plasmon resonance
Binding siteExtracellular immunoglobulin domain of TREM2
Species conservationFunctional binding observed in human, rat, and mouse systems
SpecificityCholecalciferol does not bind to related receptors (TREM1, TREML2)
KG Connections5 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (30)

TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegen
Score: 0.64
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene
Score: 0.61
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegener
Score: 0.61
TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming
Score: 0.59
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging
Score: 0.59

Related Analyses (30)

TREM2 agonism vs antagonism in DAM microglia
neurodegeneration · failed
TREM2 agonism vs antagonism in DAM microglia
neurodegeneration · archived
Immune atlas neuroinflammation analysis in neurodegeneration
Neuroinflammation · archived
Immune atlas neuroinflammation analysis in neurodegeneration
Neuroinflammation · completed
Neuroinflammation and microglial priming in early Alzheimer'
neurodegeneration · archived

Related Experiments (5)

ER-Golgi Secretory Pathway Dysfunction in PD - Experiment De
clinical · proposed · Score: 0.40
Non-Motor Symptom Progression in Parkinson's Disease — Mecha
clinical · proposed · Score: 0.40
Microglial TREM2 Agonist In Vivo Efficacy
validation · proposed · Score: 0.40
TREM2 Agonist Therapy for Parkinson's Disease — Experimental
validation · proposed · Score: 0.40
TREM2 Function in Alzheimer's Disease — From Risk Variant to
validation · proposed · Score: 0.40

See Also (7)

TREM2 Gene-Mechanism-Therapy Chain — From Genetic Risk
mechanism · Pages share 3 hypotheses
TREM2 in Frontotemporal Dementia
mechanism · Pages share 3 hypotheses
TREM2 in Amyotrophic Lateral Sclerosis
mechanism · Pages share 3 hypotheses
TREM2 Gene
gene · Pages share 3 hypotheses
al002-trem2-agonist-alzheimers
clinical_trial · Pages share 3 hypotheses

Knowledge Graph (5 edges)

ent-gene-28e2cb01 expressed_in microglia
ent-gene-28e2cb01 data_in ad_genetic_risk_loci:TREM2
ent-gene-28e2cb01 data_in benchmark_ot_ad_answer_key:TREM2
ad_genetic_risk_loci:TREM2 data_in ent-gene-28e2cb01
benchmark_ot_ad_answer_key:TREM2 data_in ent-gene-28e2cb01