Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus

Abstract

The pathological hallmarks of Alzheimer's disease (AD) include amyloid beta (A beta) accumulation, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. In this study, we investigated the neuroprotection of novel osmotin, a plant protein extracted from Nicotiana tabacum that has been considered to be a homolog of mammalian adiponectin. Here, we observed that treatment with osmotin (15 mu g/g, intraperitoneally, 4 hr) at 3 and 40 days post-intracerebroventricular injection of A beta(1-42) significantly ameliorated A beta(1-42)-induced memory impairment in mice. These results revealed that osmotin reverses A beta(1-42) injection-induced synaptic deficits, A beta accumulation and BACE-1 expression. Treatment with osmotin also alleviated the A beta(1-42)-induced hyperphosphorylation of the tau protein at serine 413 through the regulation of the aberrant phosphorylation of p-PI3K, p-Akt (serine 473) and p-GSK3 beta (serine 9). Moreover, our western blots and immunohistochemical results indicated that osmotin prevented A beta(1-42)-induced apoptosis and neurodegeneration in the A beta(1-42)-treated mice. Furthermore, osmotin attenuated A beta(1-42)-induced neurotoxicity in vitro. To our knowledge, this study is the first to investigate the neuroprotective effect of a novel osmotin against A beta(1-42)-induced neurotoxicity. Our results demonstrated that this ubiquitous plant protein could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.