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[@osborn1989]. VCAM1 is expressed predominantly on endothelial cells and is dramatically upregulated at sites of inflammation[@dustin1990].
| 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[@koning2009]:
- Signal peptide (1-19 aa): Directs protein to cell membrane
- Extracellular domain (20-698 aa): Contains 7 immunoglobulin-like (Ig) domains
- Transmembrane domain (699-723 aa): Single pass transmembrane helix
- Cytoplasmic tail (724-739 aa): Contains motifs for signaling and internalization
¶ Ig-like Domains
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)[@clements1994]. Alternative splicing can produce isoforms with 6 or 7 Ig domains[@cybulsky1991].
VCAM1 binds primarily to the integrin α4β1 (VLA-4, ITGA4/ITGB1) and α4β7[@elices1990]:
| 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 |
- Leukocyte adhesion: Mediates firm adhesion of circulating leukocytes to activated endothelium[@dustin1990]
- Extravasation: Facilitates transendothelial migration (diapedesis)[@muller2003]
- Cell survival: VCAM1-α4β1 interaction provides pro-survival signals[@mould2002]
- Angiogenesis: Supports new blood vessel formation[@garmysusini2005]
¶ Signaling and Regulation
- NF-κB: Primary transcriptional activator; VCAM1 promoter contains κB sites[@collins1995]
- AP-1: Cooperates with NF-κB for cytokine-induced expression[@iademarco1992]
- GATA: Contributes to endothelial-specific expression[@minami2004]
- STAT3: Mediates cytokine-induced upregulation[@yu2005]
- TNF-α: Strong inducer via NF-κB pathway[@osborn1989]
- IL-1β: Synergizes with TNF-α for maximal expression[@dustin1990]
- IFN-γ: Modulates VCAM1 expression in different cell types
- Shear stress: Mechanical forces regulate expression in blood vessels[@chiu2008]
- N-glycosylation: Essential for proper folding and ligand binding[@yoshida1996]
- Phosphorylation: Cytoplasmic tail phosphorylation affects signaling[@leitges2001]
- Shedding: Proteolytic cleavage produces soluble VCAM1 (sVCAM1)[@lee2006]
VCAM1 is critically involved in Alzheimer's disease pathophysiology[@grammas2011][@grammas2013]:
- BBB dysfunction: Elevated expression on brain endothelial cells contributes to blood-brain barrier breakdown[@zlokovic2008]
- Immune cell infiltration: Mediates peripheral immune cell (CD4+ T cells, monocytes) trafficking into the brain[@michaud2013]
- Cerebral amyloid angiopathy (CAA): Associated with amyloid deposition in cerebral vessels[@weller2009]
- Neurovascular unit: Dysregulation of VCAM1 disrupts endothelial-neuronal communication[@iadecola2017]
- Perivascular inflammation: Pericytes and smooth muscle cells show increased VCAM1[@blair2020]
In Parkinson's disease, VCAM1 contributes to neuroinflammation[@zhang2019][@chen2019]:
- Substantia nigra: Increased VCAM1 expression in dopaminergic regions[@mcgeer1988]
- Microglial activation: Facilitates recruitment of peripheral macrophages[@croisier2005]
- CSF biomarkers: Elevated soluble VCAM1 in cerebrospinal fluid[@hall2012]
- Disease progression: Levels correlate with Hoehn and Yahr stage[@shi2011]
- Locus coeruleus: VCAM1 expression in noradrenergic nuclei[@gesi2001]
VCAM1 is central to MS pathogenesis[@cannella1998][@engelhardt2010]:
- Immune cell trafficking: Essential for leukocyte entry into CNS[@raine1995]
- Blood-brain barrier: Critical for BBB penetration by autoreactive T cells[@vajkoczy2001]
- Lesion development: High expression in active demyelinating lesions[@sobel1993]
- Therapeutic target: Natalizumab blocks VLA-4/VCAM1 interaction[@polman2006]
¶ Stroke and Ischemic Injury
VCAM1 mediates post-ischemic inflammation[@huang2000][@wang2004]:
- Early upregulation: Rapidly induced after cerebral ischemia[@zhang1998]
- Reperfusion injury: Mediates secondary inflammatory damage[@petty2009]
- Therapeutic window: Blocking VCAM1 reduces infarct size in animal models[@vemuganti2004]
- Angiogenesis: Involved in post-stroke blood vessel repair[@hayashi2006]
VCAM1 is elevated in ALS[@zhong2008]:
- Motor cortex: Increased expression in motor cortex blood vessels[@kim2016]
- Spinal cord: Mediates inflammatory cell infiltration[@rossi2012]
- Disease progression: Correlates with rate of functional decline[@fiala2010]
- Endothelial dysfunction: Part of broader neurovascular unit disruption[@miyazaki2011]
- Endothelial cells: Low basal, highly inducible
- Epithelial cells: Variable expression
- Fibroblasts: Inducible by cytokines
- Astrocytes: Minimal under normal conditions[@rosen1992]
- Activated endothelium: Strong upregulation at sites of inflammation[@dustin1990]
- Smooth muscle cells: Inducible in pathological states[@li2010]
- Macrophages/monocytes: Express VCAM1 in inflamed tissues[@antalini1993]
- Astrocytes: Induced in reactive astrocytes (astrocytosis)[@satoh1996]
- Cerebral cortex: Low baseline, induced in pathology
- Hippocampus: Moderate expression in AD[@grammas2011]
- Basal ganglia: High expression in PD substantia nigra[@mcgeer1988]
- White matter: Associated with MS lesions[@sobel1993]
| Strategy |
Agent/Mechanism |
Development Status |
Clinical Context |
| VLA-4 Antagonists |
Natalizumab |
Approved (MS) |
Blocks α4 integrin; prevents VCAM1 binding[@polman2006] |
| VLA-4 Antagonists |
Firategrast |
Clinical trials |
Oral small molecule antagonist[@rice2005] |
| VLA-4 Antagonists |
Vedolizumab |
Approved (IBD) |
Gut-specific; not for CNS diseases |
| Blocking Antibodies |
Anti-VCAM1 antibodies |
Preclinical |
Shown to reduce immune cell infiltration[@yednock1992] |
| Small Molecules |
VCAM1-VLA-4 inhibitors |
Discovery phase |
High-throughput screening[@ref1997] |
| Gene Therapy |
siRNA targeting VCAM1 |
Preclinical |
AAV-delivered silencing[@kim2014] |
| Natural Compounds |
Curcumin, resveratrol |
Preclinical |
Downregulate VCAM1 via NF-κB[@juric2019] |
- MS treatment: Natalizumab highly effective but carries PML risk[@bloomgren2012]
- BBB modulation: VCAM1 as target for enhancing drug delivery[@nitta2003]
- Neuroprotection: Blocking VCAM1 reduces excitotoxic damage[@lawrence2003]
- Soluble VCAM1 (sVCAM1): Elevated in AD, PD, MS, stroke[@hartung1995]
- Blood/CSF ratio: Indicates CNS vs peripheral inflammation
- Disease staging: Higher levels correlate with advanced disease[@shi2011]
- Treatment monitoring: Changes reflect therapeutic response[@trojano2003]
- MS: Higher sVCAM1 predicts relapse risk[@rudick1999]
- Stroke: Elevated post-stroke VCAM1 predicts poor outcome[@castellanos2002]
- AD: VCAM1 levels predict rate of cognitive decline[@blasko2000]
- VCAM1 imaging: PET ligands for visualizing neuroinflammation[@gauberti2016]
- Single-cell analysis: VCAM1 expression in distinct immune populations[@korin2017]
- Organoid models: BBB models incorporating VCAM1 for drug testing[@brown2015]
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.
- Osborn L, et al, (1989) (1989)
- Dustin ML, et al, (1990) (1990)
- Koning GA, et al, (2009) (2009)
- Clements JM, et al, (1994) (1994)
- Cybulsky MI, et al, (1991) (1991)
- Elices MJ, et al, (1990) (1990)
- Unknown, Muller WA (2003) (2003)
- Mould AP, et al, (2002) (2002)
- Garmy-Susini B, et al, (2005) (2005)
- Collins T, et al, (1995) (1995)
- Iademarco MF, et al, (1992) (1992)
- Minami T, et al, (2004) (2004)
- Yu CL, et al, (2005) (2005)
- Chiu JJ, et al, (2008) (2008)
- Yoshida M, et al, (1996) (1996)
- Leitges M, et al, (2001) (2001)
- Lee SJ, et al, (2006) (2006)
- Grammas P, et al, (2011) (2011)
- Grammas P, et al, (2013) (2013)
- Unknown, Zlokovic BV (2008) (2008)
- Michaud JP, et al, (2013) (2013)
- Weller RO, et al, (2009) (2009)
- Unknown, Iadecola C (2017) (2017)
- Blair LJ, et al, (2020) (2020)
- Zhang Z, et al, (2019) (2019)
- Chen X, et al, (2019) (2019)
- McGeer PL, et al, (1988) (1988)
- Croisier E, et al, (2005) (2005)
- Hall S, et al, (2012) (2012)
- Shi M, et al, (2011) (2011)
- Gesi M, et al, (2001) (2001)
- Cannella B, et al, (1998) (1998)
- Engelhardt B, et al, (2010) (2010)
- Unknown, Raine CS (1995) (1995)
- Vajkoczy P, et al, (2001) (2001)
- Sobel RA, et al, (1993) (1993)
- Polman CH, et al, (2006) (2006)
- Huang J, et al, (2000) (2000)
- Wang Q, et al, (2004) (2004)
- Zhang RL, et al, (1998) (1998)
- Petty MA, et al, (2009) (2009)
- Vemuganti R, et al, (2004) (2004)
- Hayashi T, et al, (2006) (2006)
- Zhong Z, et al, (2008) (2008)
- Kim J, et al, (2016) (2016)
- Rossi D, et al, (2012) (2012)
- Fiala M, et al, (2010) (2010)
- Miyazaki K, et al, (2011) (2011)
- Rosen CL, et al, (1992) (1992)
- Li H, et al, (2010) (2010)
- antalini M, et al, (1993) (1993)
- Satoh J, et al, (1996) (1996)
- Rice GP, et al, (2005) (2005)
- Yednock TA, et al, (1992) (1992)
- 窟 Kuijper JL, et al, (1997) (1997)
- Kim ID, et al, (2014) (2014)
- Juric M, et al, (2019) (2019)
- Bloomgren G, et al, (2012) (2012)
- Nitta T, et al, (2003) (2003)
- Lawrence T, et al, (2003) (2003)
- Hartung HP, et al, (1995) (1995)
- Trojano M, et al, (2003) (2003)
- Rudick RA, et al, (1999) (1999)
- Castellanos M, et al, (2002) (2002)
- Blasko I, et al, (2000) (2000)
- Gauberti M, et al, (2016) (2016)
- Korin B, et al, (2017) (2017)
- Brown TD, et al, (2015) (2015)