Vcam1 Protein 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) is a 739-amino acid type I transmembrane glycoprotein that serves as a critical mediator of leukocyte adhesion and migration across the vascular endothelium[1]. It plays a crucial role in neuroinflammation and blood-brain barrier (BBB) dysfunction in neurodegenerative diseases. VCAM1 is predominantly expressed on activated endothelial cells and is dramatically upregulated by proinflammatory cytokines[2].
| Attribute | Value |
|---|---|
| Protein Name | Vascular Cell Adhesion Molecule 1 |
| Gene Symbol | VCAM1 |
| Protein Length | 739 amino acids |
| Molecular Weight | ~81 kDa (unglycosylated); 100-110 kDa (glycosylated) |
| UniProt ID | P19320 |
| PDB Structures | 1ASJ, 1BCZ, 1DC4, 1KV2 |
| Cellular Location | Plasma membrane (type I transmembrane) |
| Protein Family | Immunoglobulin superfamily (IgSF) |
VCAM1 contains distinct structural domains[3]:
VCAM1 binds primarily to the integrin α4β1 (VLA-4) and α4β7[5]:
| Integrin | Alternative Name | Dissociation Constant (Kd) | Expression |
|---|---|---|---|
| ITGA4/ITGB1 | VLA-4 | ~30 nM | Lymphocytes, monocytes, eosinophils |
| ITGA4/ITGB7 | α4β7 | ~100 nM | Gut-homing lymphocytes |
The D1 Ig-like domain contains the primary binding site for VLA-4, involving metal ion-dependent adhesion sites (MIDAS)[4:1].
VCAM1 is extensively N-glycosylated at multiple asparagine residues[9]:
Key structural studies reveal[4:2][11]:
The seven Ig-like domains are arranged in a linear fashion with flexible interdomain linkers, allowing simultaneous engagement of multiple ligands and receptors[12].
VCAM1 contributes significantly to AD pathogenesis[13][14]:
In PD, VCAM1 mediates neuroinflammation[20][21]:
VCAM1 is central to MS pathogenesis[26][27]:
VCAM1 mediates post-ischemic inflammation[31][32]:
VCAM1 is elevated in ALS[37]:
| Strategy | Agent | Development Status | Clinical Context |
|---|---|---|---|
| VLA-4 Antagonists | Natalizumab | Approved (MS) | Blocks α4 integrin; prevents VCAM1 binding[30:1] |
| VLA-4 Antagonists | Firategrast | Clinical trials | Oral small molecule antagonist[44] |
| VLA-4 Antagonists | Vedolizumab | Approved (IBD) | Gut-specific; not for CNS diseases |
| Blocking Antibodies | Anti-VCAM1 antibodies | Preclinical | Shown to reduce immune cell infiltration[45] |
| Small Molecules | VCAM1-VLA-4 inhibitors | Discovery phase | High-throughput screening |
| Gene Therapy | siRNA targeting VCAM1 | Preclinical | AAV-delivered silencing |
The study of Vcam1 Protein 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.
Osborn L, et al. (1989). Cell - VCAM1: an inducible endothelial adhesion molecule. PMID:2481208 ↩︎
Dustin ML, et al. (1990). J Exp Med - Induction of VCAM1 and adhesion. PMID:2121585 ↩︎ ↩︎ ↩︎
Koning GA, et al. (2009). Cell Mol Life Sci - VCAM1 structure and function. PMID:19386098 ↩︎
Clements JM, et al. (1994). J Cell Sci - VCAM1 Ig domains and binding. PMID:8006064 ↩︎ ↩︎ ↩︎
Elices MJ, et al. (1990). Cell - VLA-4 as VCAM1 receptor. PMID:1689956 ↩︎
Muller WA (2003). N Engl J Med - Leukocyte-endothelial cell interactions. PMID:12700378 ↩︎
Mould AP, et al. (2002). J Cell Biol - VCAM1 and cell survival signaling. PMID:12446740 ↩︎
Garmy-Susini B, et al. (2005). J Clin Invest - VCAM1 in angiogenesis. PMID:15937552 ↩︎
Yoshida M, et al. (1996). J Biol Chem - Glycosylation of VCAM1. PMID:8626567 ↩︎
Gough PJ, et al. (1998). J Immunol - Proteolytic shedding of VCAM1. PMID:9529303 ↩︎
Chiu NN, et al. (2001). J Mol Biol - VCAM1 structural studies. PMID:11167004 ↩︎
Wang J, et al. (2005). Structure - VCAM1 domain organization. PMID:15893701 ↩︎
Grammas P, et al. (2011). J Neuroinflammation - VCAM1 in AD. PMID:21827635 ↩︎
Iadecola C (2017). Neuron - Neurovascular unit in AD. PMID:28602638 ↩︎
Zlokovic BV (2008). Neurobiol Dis - BBB and neurovascular unit. PMID:18504134 ↩︎
Michaud JP, et al. (2013). J Neurosci - T cell trafficking in AD brain. PMID:23904614 ↩︎
Weller RO, et al. (2009). Acta Neuropathol - VCAM1 and CAA. PMID:19052761 ↩︎
Blair LJ, et al. (2020). Nat Neurosci - Pericyte VCAM1 in AD. PMID:32958947 ↩︎
Sweeney MD, et al. (2019). Nat Rev Neurol - Pericytes and BBB. PMID:31235858 ↩︎
Zhang Z, et al. (2019). Front Immunol - VCAM1 in PD. PMID:31178866 ↩︎
Chen X, et al. (2019). J Neuroinflammation - VCAM1 in PD. PMID:31064373 ↩︎
McGeer PL, et al. (1988). Neurology - VCAM1 in substantia nigra. PMID:2839804 ↩︎
Croisier E, et al. (2005). Brain - Microglial activation in PD. PMID:15816838 ↩︎
Kortekaas R, et al. (2005). Lancet Neurol - BBB dysfunction in PD. PMID:15639321 ↩︎
Shi M, et al. (2011). PLoS One - VCAM1 and PD progression. PMID:21931625 ↩︎ ↩︎
Cannella B, et al. (1998). Am J Pathol - VCAM1 in MS pathogenesis. PMID:9665969 ↩︎
Engelhardt B, et al. (2010). Nat Rev Immunol - BBB in MS. PMID:20577266 ↩︎
Raine CS (1995). Ann Neurol - Immune cell entry in MS. PMID:7644053 ↩︎
Sobel RA, et al. (1993). J Immunol - VCAM1 in MS lesions. PMID:8423348 ↩︎
Polman CH, et al. (2006). N Engl J Med - Natalizumab for MS. PMID:16428282 ↩︎ ↩︎
Huang J, et al. (2000). Brain Res - VCAM1 in stroke. PMID:10864296 ↩︎
Wang Q, et al. (2004). J Cereb Blood Flow Metab - VCAM1 after ischemia. PMID:14765195 ↩︎
Zhang RL, et al. (1998). J Cereb Blood Flow Metab - Ischemia and VCAM1. PMID:9596474 ↩︎
Petty MA, et al. (2009). Neuropharmacology - Reperfusion injury. PMID:18992725 ↩︎
Vemuganti R, et al. (2004). J Neurosci - VCAM1 blockade reduces infarct. PMID:15564593 ↩︎
Hayashi T, et al. (2006). J Cereb Blood Flow Metab - Post-stroke angiogenesis. PMID:16421508 ↩︎
Zhong Z, et al. (2008). Exp Neurol - VCAM1 in ALS. PMID:18501445 ↩︎
Kim J, et al. (2016). Acta Neuropathol Commun - Vascular inflammation in ALS. PMID:27193190 ↩︎
Rossi D, et al. (2012). Mol Cell Neurosci - VCAM1 in ALS spinal cord. PMID:22521928 ↩︎
Fiala M, et al. (2010). J Neuroinflammation - Inflammatory markers in ALS. PMID:20525206 ↩︎
Satoh J, et al. (1996). J Neuropathol Exp Neurol - Reactive astrocytes. PMID:8786408 ↩︎
Chiu JJ, et al. (2008). Arterioscler Thromb Vasc Biol - Shear stress and VCAM1. PMID:18340012 ↩︎
Khan BV, et al. (1995). Circulation - Oxidized LDL and VCAM1. PMID:7828286 ↩︎
Rice GP, et al. (2005). Neurology - Firategrast clinical trials. PMID:15928031 ↩︎
Yednock TA, et al. (1992). Nature - Anti-VCAM1 blocks disease. PMID:1329895 ↩︎
Hartung HP, et al. (1995). Ann Neurol - Soluble VCAM1 as biomarker. PMID:7668828 ↩︎
Trojano M, et al. (2003). Neurology - VCAM1 and treatment response. PMID:12963769 ↩︎