TY - JOUR
T1 - Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease
AU - Braidy, Nady
AU - Essa, Musthafa Mohamed
AU - Poljak, Anne
AU - Selvaraju, Subash
AU - Al-Adawi, Samir
AU - Manivasagm, Thamilarasan
AU - Thenmozhi, Arokiasamy Justin
AU - Ooi, Lezanne
AU - Sachdev, Perminder
AU - Guillemin, Gilles J.
PY - 2016
Y1 - 2016
N2 - Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing abnormal Amyloid Beta (Aβ) aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, microglia-dominated neuroinflammation, and impairments in synaptic plasticity underlying cognitive deficits. Therapeutic strategies for the treatment of AD are currently limited. In this study, we investigated the effects of dietary supplementation of 4% pomegranate extract to a standard chow diet on neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain. Treatment with a custom mixed diet (pellets) containing 4% pomegranate for 15 months ameliorated the loss of synaptic structure proteins, namely PSD-95, Munc18-1, and SNAP25, synaptophysin, phosphorylation of Calcium/Calmodulin Dependent Protein Kinase IIα (p-CaMKIIα/CaMKIIα), and phosphorylation of Cyclic AMP-Response Element Binding Protein (pCREB/CREB), inhibited neuroinflammatory activity, and enhanced autophagy, and activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway. These neuroprotective effects were associated with reduced β-site cleavage of Amyloid Precursor Protein in APPsw/Tg2576 mice. Therefore, long-term supplementation with pomegranates can attenuate AD pathology by reducing inflammation, and altering APP-dependent processes.
AB - Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing abnormal Amyloid Beta (Aβ) aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, microglia-dominated neuroinflammation, and impairments in synaptic plasticity underlying cognitive deficits. Therapeutic strategies for the treatment of AD are currently limited. In this study, we investigated the effects of dietary supplementation of 4% pomegranate extract to a standard chow diet on neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain. Treatment with a custom mixed diet (pellets) containing 4% pomegranate for 15 months ameliorated the loss of synaptic structure proteins, namely PSD-95, Munc18-1, and SNAP25, synaptophysin, phosphorylation of Calcium/Calmodulin Dependent Protein Kinase IIα (p-CaMKIIα/CaMKIIα), and phosphorylation of Cyclic AMP-Response Element Binding Protein (pCREB/CREB), inhibited neuroinflammatory activity, and enhanced autophagy, and activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway. These neuroprotective effects were associated with reduced β-site cleavage of Amyloid Precursor Protein in APPsw/Tg2576 mice. Therefore, long-term supplementation with pomegranates can attenuate AD pathology by reducing inflammation, and altering APP-dependent processes.
KW - Amyloid beta protein
KW - Amyloid precursor protein
KW - Gerotarget
KW - Inflammation
KW - Synapse
KW - pomegranates
UR - http://www.scopus.com/inward/record.url?scp=84994097012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994097012&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.10905
DO - 10.18632/oncotarget.10905
M3 - Article
C2 - 27486879
AN - SCOPUS:84994097012
SN - 1949-2553
VL - 7
SP - 64589
EP - 64604
JO - Oncotarget
JF - Oncotarget
IS - 40
ER -