| First Author | Parthsarathy V | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 1 | Pages | e54769 |
| PubMed ID | 23382963 | Mgi Jnum | J:195789 |
| Mgi Id | MGI:5485295 | Doi | 10.1371/journal.pone.0054769 |
| Citation | Parthsarathy V, et al. (2013) A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1DeltaE9 mouse model of Alzheimer's disease. PLoS One 8(1):e54769 |
| abstractText | Previously, we have developed a retro-inverso peptide inhibitor (RI-OR2, rGffvlkGr) that blocks the in vitro formation and toxicity of the Abeta oligomers which are thought to be a cause of neurodegeneration and memory loss in Alzheimer's disease. We have now attached a retro-inverted version of the HIV protein transduction domain 'TAT' to RI-OR2 to target this new inhibitor (RI-OR2-TAT, Ac-rGffvlkGrrrrqrrkkrGy-NH(2)) into the brain. Following its peripheral injection, a fluorescein-labelled version of RI-OR2-TAT was found to cross the blood brain barrier and bind to the amyloid plaques and activated microglial cells present in the cerebral cortex of 17-months-old APPswe/PS1DeltaE9 transgenic mice. Daily intraperitoneal injection of RI-OR2-TAT (at 100 nmol/kg) for 21 days into 10-months-old APPswe/PS1DeltaE9 mice resulted in a 25% reduction (p<0.01) in the cerebral cortex of Abeta oligomer levels, a 32% reduction (p<0.0001) of beta-amyloid plaque count, a 44% reduction (p<0.0001) in the numbers of activated microglial cells, and a 25% reduction (p<0.0001) in oxidative damage, while the number of young neurons in the dentate gyrus was increased by 210% (p<0.0001), all compared to control APPswe/PS1DeltaE9 mice injected with vehicle (saline) alone. Our data suggest that oxidative damage, inflammation, and inhibition of neurogenesis are all a downstream consequence of Abeta aggregation, and identify a novel brain-penetrant retro-inverso peptide inhibitor of Abeta oligomer formation for further testing in humans as a potential disease-modifying treatment for Alzheimer's disease. |
