Furthermore, siRNA knockdown of IL17RC was sufficient to rescue ARPE-19 viability in the presence of IL17A associated with significant reductions in caspase activation. The ultimate goal of the present study was to evaluate the therapeutic potential of IL17A knockdown in a preclinical retinal degeneration model. Our lab has generated a mouse model of focal retinal degeneration that undergoes progressive retinal degeneration beginning as early as 2�C3 weeks after birth. Since the BBB poses a serious obstacle to delivering therapeutics to the brain, a damaged BBB associated with brain tumors provides a common avenue for delivering chemotherapeutics. However, the BBB is only marginally disrupted in grade 2 and 3 gliomas. Furthermore, in grade 4 BRL 50481 gliomas the BBB damage is limited to the area of vascular damage. In all gliomas neoplastic tumor cells have widely invaded well beyond the region of obvious radiologic involvement. Thus it has been argued that novel methods are urgently needed that can enhance drug delivery throughout the brain beyond the level obtained via a damaged BBB. The BBB harbors receptors that allow transport of cognate protein ligands from the vasculature to the brain through transcytosis. Several investigators have utilized such ligand-receptor systems to develop strategies for delivering various proteins to the brain. However, all these methods employ covalent linking of the target proteins to a peptide carrier comprised of the receptor-binding domain of a ligand, an antibody against a receptor or to other peptides and proteins deemed to have BBB transport activity. Covalent linking of a carrier entity to a protein ��load�� involves complex issues such as expertise in linkage chemistry, necessity of purification after linkage, evaluation of functionality after purification etc. Incorporating a given drug into BBB-penetrating Flecainide acetate nanoparticles also requires considerable efforts to formulate the nanoparticles harboring the drug of choice and a separate method such as CED to deliver the nanoparticles across the BBB. Consequently, we sought to develop noncovalent brain delivery methods of therapeutic agents that would avoid these limitations. We have recently reported creation of a carrier peptide that transported various proteins and immunoglobulins across the BBB in a non-covalent manner. Since cancer therapeutics comprise both large and small-molecule agents, we explored if the carrier peptide would also enable non-covalent delivery of ��small molecules�� to the brain. Based on our previous work we hypothesized that the ApoE-like protein-K16ApoE complex causes conformational change of LDLR-expressing cells at the BBB creating transient pores through which passive transport of other molecules to the brain can take place.