Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9 -/-), DOCK10 (DOCK10 -/-), or DOCK11 (DOCK11 -/-) had been deleted and examined the phenotypic effects of these gene deletions in MOG35-55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10 -/- mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10 -/- and DOCK11 -/- mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10 -/- mice. No apparent phenotype was observed for DOCK9 -/- mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10 -/- mice. Up-regulation of C-C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10 -/- astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.
 ...
PMID:Roles of the DOCK-D family proteins in a mouse model of neuroinflammation. 3224 15