Vcam1 Vascular Cell Adhesion Molecule 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Vascular Cell Adhesion Molecule 1 (VCAM1) encodes a cell surface glycoprotein essential for leukocyte adhesion and migration across the vascular endothelium. It plays a crucial role in neuroinflammation and blood-brain barrier (BBB) dysfunction in neurodegenerative diseases[1]. VCAM1 is expressed predominantly on endothelial cells and is dramatically upregulated at sites of inflammation[2].
| Attribute | Value |
|---|---|
| Gene Symbol | VCAM1 |
| Official Name | Vascular Cell Adhesion Molecule 1 |
| Chromosomal Location | 1p21.2 |
| Gene ID | 7412 |
| NCBI Reference | NM_001078 |
| UniProt | P19320 |
| Ensembl | ENSG00000162692 |
VCAM1 is a type I transmembrane glycoprotein with distinctive structural features[3]:
The seven Ig-like domains (D1-D7) each contain conserved cysteine residues forming disulfide bonds. The N-terminal D1 domain contains the binding site for the integrin α4β1 (VLA-4)[4]. Alternative splicing can produce isoforms with 6 or 7 Ig domains[5].
VCAM1 binds primarily to the integrin α4β1 (VLA-4, ITGA4/ITGB1) and α4β7[6]:
| Integrin | Alternative Name | Expression | Function |
|---|---|---|---|
| ITGA4/ITGB1 | VLA-4 | Lymphocytes, monocytes, eosinophils, basophils | Primary VCAM1 receptor |
| ITGA4/ITGB7 | α4β7 | Gut-homing lymphocytes | Mucosal immune regulation |
VCAM1 is critically involved in Alzheimer's disease pathophysiology[18][19]:
In Parkinson's disease, VCAM1 contributes to neuroinflammation[25][26]:
VCAM1 is central to MS pathogenesis[32][33]:
VCAM1 mediates post-ischemic inflammation[38][39]:
VCAM1 is elevated in ALS[44]:
| Strategy | Agent/Mechanism | Development Status | Clinical Context |
|---|---|---|---|
| VLA-4 Antagonists | Natalizumab | Approved (MS) | Blocks α4 integrin; prevents VCAM1 binding[37:1] |
| VLA-4 Antagonists | Firategrast | Clinical trials | Oral small molecule antagonist[53] |
| VLA-4 Antagonists | Vedolizumab | Approved (IBD) | Gut-specific; not for CNS diseases |
| Blocking Antibodies | Anti-VCAM1 antibodies | Preclinical | Shown to reduce immune cell infiltration[54] |
| Small Molecules | VCAM1-VLA-4 inhibitors | Discovery phase | High-throughput screening[55] |
| Gene Therapy | siRNA targeting VCAM1 | Preclinical | AAV-delivered silencing[56] |
| Natural Compounds | Curcumin, resveratrol | Preclinical | Downregulate VCAM1 via NF-κB[57] |
The study of Vcam1 Vascular Cell Adhesion Molecule 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
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