Neurodegenerative diseases generate the accumulation of specific misfolded proteins, such as PrPSc prions or A-beta in Alzheimer's diseases, and share common pathological features, like neuronal death and oxidative damage. To test whether reduced oxidation alters disease manifestation, we treated TgMHu2ME199K mice, modeling for genetic prion disease, with Nano-PSO, a nanodroplet formulation of pomegranate seed oil (PSO). PSO comprises large concentrations of a unique polyunsaturated fatty acid, Punicic acid, among the strongest natural antioxidants. Nano-PSO significantly delayed disease presentation when administered to asymptomatic TgMHu2ME199K mice and postponed disease aggravation in already sick mice. Analysis of brain samples revealed that Nano-PSO treatment did not decrease PrPSc accumulation, but rather reduced lipid oxidation and neuronal loss, indicating a strong neuroprotective effect. We propose that Nano-PSO and alike formulations may be both beneficial and safe enough to be administered for long years to subjects at risk or to those already affected by neurodegenerative conditions.From the Clinical Editor This team of authors report that a nanoformulation of pomegranade seed oil, containing high levels of a strong antioxidant, can delay disease onset in a mouse model of genetic prion diseases, and the formulation also indicates a direct neuroprotective effect.
Accession Number: S1549963414001336; Author: Mizrahi, Michal (a, 1); Author: Friedman-Levi, Yael (a, 1); Author: Larush, Liraz (b); Author: Frid, Kati (a); Author: Binyamin, Orli (a); Author: Dori, Dvir (a); Author: Fainstein, Nina (a); Author: Ovadia, Haim (a); Author: Ben-Hur, Tamir (a); Author: Magdassi, Shlomo (b); Author: Gabizon, Ruth (a, ⁎); Affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel; Affiliation: Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel; Funding: This project was funded by a grant from the Israel Science Foundation (ISF) and by the Agnes Ginges Center. At present time, a commercial entity (Granalix) is being formed based on the presented results; Number of Pages: 11; Language: English;