D description in the CPP internalization mechanisms, along with other properties which include stability, toxicity and immunogenicity were reviewed elsewhere [199]. Here we focus on use of CPPs for delivery of CD200R Proteins Accession proteins to CNS. Schwarze and colleagues published a seminal perform demonstrating ability of CPP to provide proteins across BBB [200]. In their study the NH2-terminal TAT (477)-galactosidase fusion protein (120 kDa) injected i.p. in mice was detected by immunochemical staining initially at 2 hr in brain microvessels after which at 4 hr in brain parenchyma. No PK studies had been performed. Nonetheless galactosidase activity was visualized in CD150 Proteins Biological Activity sagittal and coronal brain sections too as in liver, kidney, lung and heart (myocardium) and spleen. TAT did not appear to disrupt BBB as the Evan’s blue albumin complexes co-injected with TAT were excluded from the brain tissues. Subsequently, TAT peptide was fused with GDNF and injected i.p. within a mouse model of PD. The fusion protein crossed the BBB and reached substantia nigra as was shown by immunohistochemical staining. However, the treatment did not prevent the loss of dopaminergic neurons in PD mice, possibly since the quantity of the fusion protein delivered to the target site was not enough [201]. A TAT-based method was also used to provide Bcl-xL protein, a well-characterized death-suppression molecule, towards the CNS for treatment of stroke. Intraperitoneal injection of TAT and Bcl-xL fusion protein resulted in a robust protein transduction in neurons, as well as a dose-dependent decrease of cerebral infarction in a mouse middle cerebral artery occlusion (MCAO) model of ischemic stroke [202]. Similarly, a reduced infarct volume and neurological deficits had been observed following i.v. injection of TAT-Bcl-xL fusion protein 1 hr. before or straight away just after the ischemia induced inside a rat MCAO model [203]. A current study reported that TAT-leptin fusion protein was i.v. injected to mice fed with high-fat eating plan. Immunohistochemical stainingNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptJ Manage Release. Author manuscript; readily available in PMC 2015 September 28.Yi et al.Pagesuggested improve in leptin accumulation in hypothalamus inside the TAT-leptin treated mice, compared to the unmodified leptin or saline-treated animals. Importantly, TAT-leptin also prevented body-weight obtain much more efficiently compared to leptin [204]. Cai et al. lately described good effects of TAT-mediated delivery of neuroglobin (Ngb) on focal cerebral ischemia outcome in mice [205]. Immediately after i.v. injection the TAT-Ngb fusion protein was detected in mice brain tissues by immunohistochemistry and western blotting. The group treated with TAT-Ngb 2 hr. just before MCAO showed smaller sized brain infarct volume and enhanced neurologic outcomes when compared with the control groups. Furthermore, the group treated with TAT-Ngb immediately after MCAO and reperfusion showed substantially enhanced neuronal survival within the striatum, when compared with the controls [205]. In addition to TAT some other CPPs, which include Syn-B vectors and Rabies virus glycoproteinderived peptide (RDP), had been also shown to provide compact molecules and proteins across BBB [206, 207]. For example, Xiang et al reported effective hippocampus targeting by a galactosidase-RDP fusion protein [206]. Interestingly, a basic mixing of a protein with CPP also improved delivery of several proteins including -galactosidase, human IgG and IgM to mouse brain [208]. Even so, CPP have displayed numerous toxicities includin.
