Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD.
Neurodegenerative diseases generate the accumulation of specific misfolded proteins, such as PrP(Sc) 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 PrP(Sc) 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.


BACKGROUND
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.
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Michal
M
Mizrahi
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Yael
Y
Friedman-Levi
Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Liraz
L
Larush
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Kati
K
Frid
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Orli
O
Binyamin
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Dvir
D
Dori
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Nina
N
Fainstein
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Haim
H
Ovadia
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Tamir
T
Ben-Hur
Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shlomo
S
Magdassi
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel. Electronic address: gabizonr@hadassah.org.il.
Ruth
R
Gabizon
D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004655:Emulsions / Q000737:chemistry / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D029561:Lythraceae / Q000737:chemistry*; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D010938:Plant Oils / Q000737:chemistry / Q000627:therapeutic use*; D011328:Prions / Q000378:metabolism; D012639:Seeds / Q000737:chemistry
D004655:Emulsions; D018696:Neuroprotective Agents; D010938:Plant Oils; D011328:Prions
Nanoparticles; Neurodegeneration; Oxidation; PSO; Prion