IRIS – Institutional Research Information System
IRIS è il sistema di gestione della ricerca dell’Università degli Studi di Milano-Bicocca.Il repository BOA è il modulo del sistema dedicato alla raccolta e alla disseminazione della produzione scientifica di Ateneo. Le pubblicazioni sono ricercabili per parola chiave attraverso il box nella barra orizzontale in alto oppure, mediante il pulsante Sfoglia, per "Afferenza", "Autore", "Titolo", "Tipologia" o "Settore scientifico-disciplinare".
IRIS contiene inoltre alcuni moduli dedicati alla registrazione dei progetti e dei contratti, e alla reportistica avanzata per le attività di valutazione della ricerca
EnglishPreviously, we have developed a retro-inverso peptide inhibitor (RI-OR2, rGffvlkGr) that blocks the in vitro formation and toxicity of the Aβ 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-NH2) 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/PS1ΔE9 transgenic mice. Daily intraperitoneal injection of RI-OR2-TAT (at 100 nmol/kg) for 21 days into 10-months-old APPswe/PS1ΔE9 mice resulted in a 25% reduction (p<0.01) in the cerebral cortex of Aβ oligomer levels, a 32% reduction (p<0.0001) of β-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/PS1ΔE9 mice injected with vehicle (saline) alone. Our data suggest that oxidative damage, inflammation, and inhibition of neurogenesis are all a downstream consequence of Aβ aggregation, and identify a novel brain-penetrant retro-inverso peptide inhibitor of Aβ oligomer formation for further testing in humans as a potential disease-modifying treatment for Alzheimer's disease. © 2013 Parthsarathy et al.
Parthsarathy, V., McClean, P., Holscher, C., Taylor, M., Tinker, C., Jones, G., et al. (2013). A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1 Delta E9 Mouse Model of Alzheimer's Disease. PLOS ONE, 8(1) [10.1371/journal.pone.0054769].
| Citazione: | Parthsarathy, V., McClean, P., Holscher, C., Taylor, M., Tinker, C., Jones, G., et al. (2013). A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1 Delta E9 Mouse Model of Alzheimer's Disease. PLOS ONE, 8(1) [10.1371/journal.pone.0054769]. | |
| Tipo: | Articolo in rivista - Articolo scientifico | |
| Carattere della pubblicazione: | Scientifica | |
| Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
| Titolo: | A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1 Delta E9 Mouse Model of Alzheimer's Disease | |
| Autori: | Parthsarathy, V; McClean, P; Holscher, C; Taylor, M; Tinker, C; Jones, G; Kolosov, O; Salvati, E; Gregori, M; Masserini, ME; Allsop, D | |
| Autori: | ||
| Data di pubblicazione: | 2013 | |
| Lingua: | English | |
| Rivista: | PLOS ONE | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1371/journal.pone.0054769 | |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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