Use of cell permeable NBD peptides for suppression of inflammation.
Nuclear factor (NF)-kappaB is a ubiquitous and essential transcription factor whose dysregulation has been linked to numerous diseases including arthritis and cancer. It is therefore not surprising that the NF-kappaB activation pathway has become a major target for development of novel therapies for inflammatory diseases and cancer. However, the indispensable role played by NF-kappaB in many biological processes has raised concern that a complete shutdown of this pathway would have significant detrimental effects on normal cellular function. Instead, drugs that selectively target the inflammation induced NF-kappaB activity, while sparing the protective functions of basal NF-kappaB activity, would be of greater therapeutic value and would likely display fewer undesired side effects. The recent identification and characterisation of the NF-kappaB essential modulator (NEMO)-binding domain (NBD) peptide that can block the activation of the IkappaB kinase (IKK) complex, have provided an opportunity to selectively abrogate the inflammation induced activation of NF-kappaB by targeting the NBD-NEMO interaction. This peptide is synthesised in tandem with a protein transduction domain sequence from Drosophila antennapedia which facilitates uptake of the inhibitory peptide into the cytosol of target cells.
Strickland
I
I
Section of Immunology, Department of Biophysics and Biochemistry, Yale University, New Haen, CT, USA.
Ghosh
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D010455:Peptides / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; C467063:NBD peptide, mouse; D016328:NF-kappa B; D010455:Peptides; D051550:I-kappa B Kinase