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 journalArticle

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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
LanguageEnglish
Pagese54769
JournalPLoS ONE
Volume8
Issue number1
DOIs
Publication statusPublished - 2013

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Human Immunodeficiency Virus Proteins
neurogenesis
Neurogenesis
Amyloid Plaques
Memory Disorders
Corrosion inhibitors
amyloid
Alzheimer disease
Intraperitoneal Injections
Blood-Brain Barrier
Fluorescein
Oligomers
Amyloid
Cerebral Cortex
Transgenic Mice
Toxicity
Brain
Alzheimer Disease
inflammation
animal models

Cite this

Parthsarathy, Vadivel ; McClean, Paula ; Hölscher, Christian ; Taylor, Mark ; Tinker, Claire ; Jones, Glynn ; Kolosov, Oleg ; Salvati, Elisa ; Gregori, Maria ; Masserini, Massimo ; Allsop, David. / 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. In: PLoS ONE. 2013 ; Vol. 8, No. 1. pp. e54769.
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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

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

In: PLoS ONE, Vol. 8, No. 1, 2013, p. e54769.

Research output: Contribution to journalArticle

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