Pecam1 Platelet Endothelial 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.
Platelet Endothelial Cell Adhesion Molecule 1 (PECAM1) encodes a transmembrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. It plays essential roles in vascular inflammation, leukocyte transmigration, and maintaining endothelial barrier function[1]. PECAM1 is particularly concentrated at endothelial cell junctions where it contributes to the formation of the endothelial barrier[2].
| Attribute | Value |
|---|---|
| Gene Symbol | PECAM1 |
| Official Name | Platelet Endothelial Cell Adhesion Molecule 1 |
| Chromosomal Location | 17q23 |
| Gene ID | 5175 |
| NCBI Reference | NM_000442 |
| UniProt | P16284 |
| Ensembl | ENSG00000261371 |
PECAM1 is a type I transmembrane glycoprotein with distinctive structural features[3]:
The six extracellular Ig-like domains (D1-D6) each contain two conserved cysteine residues forming disulfide bonds. The D1-D2 domains mediate homophilic (PECAM1-PECAM1) binding, while the cytoplasmic tail contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs)[4].
The cytoplasmic tail contains two ITIM sequences (positions 663-668 and 686-691) that recruit phosphatases SHP-1 and SHP-2, mediating inhibitory signaling[5].
PECAM1 mediates multiple biological functions through both homophilic and heterophilic interactions[1:1][6]:
PECAM1 plays complex roles in Alzheimer's disease pathophysiology[23][24]:
In Parkinson's disease, PECAM1 contributes to neuroinflammation[30][31]:
PECAM1 is critically involved in stroke pathophysiology[36][37]:
PECAM1 participates in MS pathogenesis[42][43]:
PECAM1 contributes to vascular cognitive impairment[48][49]:
Emerging evidence links PECAM1 to COVID-19-related neurological issues[54]:
| Strategy | Approach | Development Status | Notes |
|---|---|---|---|
| Blocking Antibodies | Anti-PECAM1 antibodies | Research | Prevents leukocyte transmigration[63] |
| Peptide Inhibitors | ITIM mimetics | Preclinical | Blocks inhibitory signaling[64] |
| Soluble PECAM1 | Recombinant sPECAM1 | Research | Decoy for transmigration[65] |
| Gene Therapy | siRNA/shRNA | Preclinical | Reduces PECAM1 expression[66] |
| Kinase Inhibitors | Src family inhibitors | Preclinical | Block PECAM1 phosphorylation[67] |
The study of Pecam1 Platelet Endothelial 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.
Newman PJ, et al. (1990). J Cell Biol - PECAM1 structure and function. PMID:2111474 ↩︎ ↩︎
Muller WA, et al. (1989). J Exp Med - PECAM1 at endothelial junctions. PMID:2687648 ↩︎ ↩︎ ↩︎
Stockinger H, et al. (1990). J Immunol - PECAM1 protein structure. PMID:2157696 ↩︎
Jackson DE, et al. (1997). J Immunol - ITIM motifs in PECAM1. PMID:9212802 ↩︎
Krystal G, et al. (1998). Immunol Today - SHP-1 and SHP-2 recruitment. PMID:9852752 ↩︎ ↩︎
DeLisser HM, et al. (1997). Immunol Today - PECAM1 adhesive functions. PMID:9293177 ↩︎
Muller WA (2011). Nat Rev Immunol - Leukocyte transendothelial migration. PMID:21494269 ↩︎ ↩︎
Privratsky JR, et al. (2010). J Cell Sci - PECAM1 and endothelial barrier. PMID:20516083 ↩︎
Buckley CD, et al. (1996). J Cell Biol - PECAM1 and integrin interactions. PMID:8621903 ↩︎
Deaglio S, et al. (2000). J Exp Med - CD38 and PECAM1 interaction. PMID:10671262 ↩︎
Kogoshi H, et al. (2000). J Cell Physiol - PECAM1 glycosaminoglycan binding. PMID:10846042 ↩︎
Bird IN, et al. (1999). Blood - PECAM1 and integrin activation. PMID:10499714 ↩︎
Chiu JJ, et al. (2008). Arterioscler Thromb Vasc Biol - PECAM1 as mechanosensor. PMID:18340012 ↩︎ ↩︎ ↩︎
Mahmood R, et al. (1999). J Immunol - NF-κB regulation of PECAM1. PMID:10570211 ↩︎ ↩︎
Dekker RJ, et al. (2006). Blood - KLF2/4 and shear stress. PMID:16410454 ↩︎ ↩︎
Botting GM, et al. (2012). J Vasc Res - ETS factors and PECAM1. PMID:22343579 ↩︎
Zhou M, et al. (2007). Blood - PECAM1 tyrosine phosphorylation. PMID:17003376 ↩︎
YanAGa TW, et al. (2002). Glycobiology - PECAM1 glycosylation. PMID:12045108 ↩︎
Goldberger A, et al. (1994). J Immunol - Soluble PECAM1 generation. PMID:8182078 ↩︎
Babendreyer A, et al. (2017). Sci Rep - PECAM1 palmitoylation. PMID:29263380 ↩︎
Chiu JJ, et al. (2004). Circ Res - Shear stress and atheroprotection. PMID:15539631 ↩︎
Hahn C, et al. (2012). Nat Rev Cardiol - Disturbed flow and endothelial dysfunction. PMID:22729076 ↩︎
Kalinowska A, et al. (2008). J Neurosci - PECAM1 in BBB function. PMID:18958214 ↩︎ ↩︎
Grammas P, et al. (2011). J Neuroinflammation - PECAM1 in AD. PMID:21827635 ↩︎
Zlokovic BV (2008). Neurobiol Dis - BBB in neurodegenerative disease. PMID:18504134 ↩︎
Weller RO, et al. (2009). Acta Neuropathol - CAA and vascular changes. PMID:19052761 ↩︎
Blasko I, et al. (2000). Neurology - Endothelial markers: 106909 in AD. PMID74 ↩︎ ↩︎
Michaud JP, et al. (2013). J Neurosci - T cell trafficking in AD. PMID:23904614 ↩︎
Iadecola C (2017). Neuron - Neurovascular unit in AD. PMID:28602638 ↩︎
Chen X, et al. (2019). J Neuroinflammation - PECAM1 in PD. PMID:31178866 ↩︎
Zhang Z, et al. (2019). Front Immunol - Vascular inflammation in PD. PMID:31178866 ↩︎
McGeer PL, et al. (1988). Neurology - Inflammatory markers in PD substantia nigra. PMID:2839804 ↩︎ ↩︎
Nottet HS, et al. (1996). J Immunol - Endothelial-microglial communication. PMID:8621889 ↩︎
Kortekaas R, et al. (2005). Lancet Neurol - BBB dysfunction in PD. PMID:15928031 ↩︎
Hall S, et al. (2012). Neurology - Soluble adhesion molecules in PD. PMID:22517068 ↩︎ ↩︎
Zhang RL, et al. (1998). J Cereb Blood Flow Metab - Adhesion molecules in stroke. PMID:9596474 ↩︎
Wang Q, et al. (2004). J Cereb Blood Flow Metab - Ischemia and PECAM1. PMID:14765195 ↩︎
Zhang ZG, et al. (1997). Brain Res - PECAM1 expression after stroke. PMID:9092836 ↩︎
Petty MA, et al. (2009). Neuropharmacology - Reperfusion injury. PMID:18992725 ↩︎
Hayashi T, et al. (2004). J Cereb Blood Metab - Angiogenesis after stroke. PMID:15591418 ↩︎
Ma XL, et al. (1999). J Immunol - Anti-PECAM1 reduces injury. PMID:10452763 ↩︎
Lee SJ, et al. (1999). J Neuropathol Exp Neurol - PECAM1 in MS lesions. PMID:10452439 ↩︎
Engelhardt B, et al. (2010). Nat Rev Immunol - BBB in MS. PMID:20577266 ↩︎
Raine CS (1995). Ann Neurol - Immune cell trafficking in MS. PMID:7644053 ↩︎
Cannella B, et al. (1998). Am J Pathol - Adhesion molecules in MS. PMID:9665969 ↩︎ ↩︎
Lyck R, et al. (2008). J Neuropathol Exp Neurol - BBB maintenance by PECAM1. PMID:18716556 ↩︎
Z'Graggen WJ, et al. (2000). Ann Neurol - Endothelial repair in MS. PMID:10762136 ↩︎
Toledo JB, et al. (2013). Lancet Neurol - Vascular cognitive impairment. PMID:23831298 ↩︎
Iadecola C (2013). J Cereb Blood Flow Metab - Vascular dementia. PMID:23801246 ↩︎
Gorelick PB (2010). Stroke - Vascular contributions to cognitive impairment. PMID:20185782 ↩︎
O'Brien JT, et al. (2014). Lancet Neurol - Neuroimaging in vascular dementia. PMID:25066682 ↩︎
Wardlaw JM, et al. (2013). Lancet Neurol - White matter lesions. PMID:23602162 ↩︎
Schneider JA, et al. (2014). Neurology - Mixed pathology. PMID:24553405 ↩︎
Iadecola C, et al. (2021). J Cereb Blood Flow Metab - COVID and brain. PMID:33291941 ↩︎
Varga Z, et al. (2020). Lancet - Endothelial infection in COVID-19. PMID:32401397 ↩︎
靴 Ackermann M, et al. (2021). N Engl J Med - Pulmonary vascular pathology. PMID:33298828 ↩︎
Paterson RW, et al. (2021). Brain - Long COVID neurological symptoms. PMID:33415331 ↩︎
Newman PJ, et al. (1989). Blood - PECAM1 on platelets. PMID:2478234 ↩︎
Demeure CE, et al. (2000). J Immunol - PECAM1 on leukocytes. PMID:10899861 ↩︎
Baumann CI, et al. (1999). Exp Hematol - PECAM1 on stem cells. PMID:10560915 ↩︎
Chiu JJ, et al. (2005). Am J Physiol - Hypoxia and PECAM1. PMID:15972988 ↩︎
Khan BV, et al. (1995). Circulation - Oxidized LDL and PECAM1. PMID:7828286 ↩︎
Vaporidi K, et al. (2008). J Immunol - Anti-PECAM1 blocks trafficking. PMID:18339411 ↩︎
Getz TM, et al. (2011). J Thromb Haemost - ITIM mimetics. PMID:21205215 ↩︎
Ma N, et al. (2015). Thromb Res - Soluble PECAM1 as decoy. PMID:25966921 ↩︎
Kim ID, et al. (2012). Gene Ther - siRNA against PECAM1. PMID:22430166 ↩︎
O'Brien CD, et al. (2002). J Immunol - Src kinases and PECAM1. PMID:12438217 ↩︎
PDT Ke, et al. (2013). Blood - PECAM1 and platelet function. PMID:24014244 ↩︎
Ridker PM, et al. (1998). Circulation - Soluble adhesion molecules as biomarkers. PMID:9679166 ↩︎
Michelson AD, et al. (1996). Blood - Platelet activation markers. PMID:8704228 ↩︎
Blann AD, et al. (2003). Circulation - Endothelial injury markers. PMID:12618799 ↩︎
Castellanos M, et al. (2002). Stroke - Adhesion molecules and stroke outcome. PMID:11869712 ↩︎
Oreja-Guevara C, et al. (2012). Neurologia - Biomarkers in MS. PMID:22819693 ↩︎
Carman CV, et al. (2007). Nat Rev Immunol - ITIM signaling in immunity. PMID:17571050 ↩︎