A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

Vadivel Parthsarathy; Paula McClean; Christian Hölscher; Mark Taylor; Claire Tinker; Glynn Jones; Oleg Kolosov; Elisa Salvati; Maria Gregori; Massimo Masserini; David Allsop

doi:10.1371/journal.pone.0054769

A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

Vadivel Parthsarathy, Paula McClean, Christian Hölscher, Mark Taylor, Claire Tinker, Glynn Jones, Oleg Kolosov, Elisa Salvati, Maria Gregori, Massimo Masserini, David Allsop

Research output: Contribution to journal › Article › peer-review

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Abstract

Previously, 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-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/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

Original language	English
Pages (from-to)	e54769
Journal	PLoS ONE
Volume	8
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0054769
Publication status	Published (in print/issue) - 2013

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Parthsarathy, V., McClean, P., Hölscher, C., Taylor, M., Tinker, C., Jones, G., Kolosov, O., Salvati, E., Gregori, M., Masserini, M., & Allsop, D. (2013). A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. PLoS ONE, 8(1), e54769. https://doi.org/10.1371/journal.pone.0054769

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abstract = "Previously, 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-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/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",

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Parthsarathy, V, McClean, P, Hölscher, C, Taylor, M, Tinker, C, Jones, G, Kolosov, O, Salvati, E, Gregori, M, Masserini, M & Allsop, D 2013, 'A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.', PLoS ONE, vol. 8, no. 1, pp. e54769. https://doi.org/10.1371/journal.pone.0054769

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AU - Tinker, Claire

AU - Jones, Glynn

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AU - Salvati, Elisa

AU - Gregori, Maria

AU - Masserini, Massimo

AU - Allsop, David

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A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

Abstract

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