Among these, four curcumin target

Among these, four curcumin target during genes are related to cell migration. Netrin G1 is a lipid anchored protein that is structurally related to the netrin family of axon guidance molecules. It regulates synaptic interac tions between neurons by binding Inhibitors,Modulators,Libraries to transmembrane netrin G ligands. Interestingly, the related Netrin 1 molecule is a broad inhibitor of leukocyte chemotaxis and Netrin G1 may have a similar function Inhibitors,Modulators,Libraries in microglia. The adhesion molecule PECAM1 is also directly involved in monocyte macrophage migration. Another migration related gene induced by curcumin is Plasma cell endoplasmic reti culum protein 1. PERP 1 is a molecular chaperone required for proper folding and secretion of immunoglobulins in B cells. Related to our study, a recent report linked PERP 1 to calcium signaling, activation of integrins and cell adhesion.

Expression of the Notch ligand Delta like 1 has been demonstrated in BV 2 cells and primary rat brain microglial cells, where Inhibitors,Modulators,Libraries Notch 1 sig naling negatively regulates TNF release. Our data show that basal Dll1 expression in resting microglial cells can be potently induced by curcumin, which could potentially trig ger Notch signaling to prevent migration associated with pro inflammatory priming of BV 2 cells. These transcriptomic data of curcumin treatment pro moted us to analyze its effects on microglial motility. Both types of assays, the wound healing assays and the transwell migration experiments, showed that BV 2 cell migration was significantly inhibited by 20 uM curcumin over a period of 12 hours to 24 hours.

These findings are in good agreement Inhibitors,Modulators,Libraries with papers reporting reduced migra tion of tumor cells, endothelial cells, and dendritic cells after treatment with comparable doses of cucumin. In the homeostatic state, microglia constantly scan their environment with their long protrusions with out movement of the somata. In contrast, migration of microglial cells is a hallmark of pro inflammatory and chronic activation during early phases of neurodegenera tion. Thus, curcumin may support the homeostatic state of microglia and prevent their early and excessive trans formation into migrating phagocytes. It is well known that curcumin broadly inhibits pro inflammatory gene expression by targeting different sig nal pathways and transcriptional regulators including NFkB, AP1, EGR1, and STAT3.

Our microarray data corroborate these findings especially in LPS activated BV 2 cells by showing curcumin triggered suppression of Ptgs2, Ccl2, Il6, and Nos2, which are NFkB, AP1, and STAT3 target genes. Moreover, the curcumin regu lated transcriptomic Inhibitors,Modulators,Libraries profiles revealed lower gene expres sion of toll like receptor 2 in resting microglia and complement factor 3 in activated cells. These two factors broadly support the conversion sellectchem of microglial cells to the pro inflammatory state and hence curcumin sig naling may abrogate both pathways.

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