Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls. Passive EAE transfer experiments suggested that the pathophysiology observed in active EAE was linked to the absence of ALCAM on BBB-ECs. In addition, phenotypic characterization of unimmunized ALCAM KO mice revealed a reduced expression of BBB junctional proteins. Further in vivo, in vitro, and molecular analysis confirmed that ALCAM is associated with tight junction molecule assembly at the BBB, explaining the increased permeability of CNS blood vessels in ALCAM KO animals. Collectively, our data point to a biologically important function of ALCAM in maintaining BBB integrity.
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http://dx.doi.org/10.1073/pnas.1614336114 | DOI Listing |
IET Syst Biol
December 2024
Institute of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
BMC Gastroenterol
November 2024
Department of Gastroenterology, Shaanxi Provincial People's Hospital, No. 256 Friendship West Road, Beilin District, Xi'an, Shaanxi, 710068, China.
Mol Neurobiol
November 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Secreted and membrane-tethered mammalian neuromodulators from the Ly6/uPAR family are involved in regulation of many physiological processes. Some of them are expressed in the CNS in the neurons of different brain regions and target neuronal membrane receptors. Thus, Lynx1 potentiates nicotinic acetylcholine receptors (nAChRs) in the brain, while others like Lypd6 and Lypd6b suppress it.
View Article and Find Full Text PDFFront Cell Dev Biol
October 2024
School of Biopharmacy, China Pharmaceutical University, Nanjing, China.
Background: Characterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.
View Article and Find Full Text PDFMov Disord
November 2024
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Background: The age at onset (AAO) of Parkinson's disease (PD) varies widely among individuals and significantly influences disease progression and prognosis. However, few genome-wide association studies (GWASs) have investigated genetic variants determining AAO, particularly in East Asian populations.
Objectives: To identify single-nucleotide polymorphisms (SNPs) affecting AAO of PD in Korean patients.
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