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

Abstract

The pathological hallmarks of Alzheimera € s disease (AD) include amyloid beta (Aβ) 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 (15a €‰I 1/4g/g, intraperitoneally, 4a €‰hr) at 3 and 40 days post-intracerebroventricular injection of Aβ 1-42 significantly ameliorated Aβ 1-42 -induced memory impairment in mice. These results revealed that osmotin reverses Aβ 1-42 injection-induced synaptic deficits, Aβ accumulation and BACE-1 expression. Treatment with osmotin also alleviated the Aβ 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-GSK3β (serine 9). Moreover, our western blots and immunohistochemical results indicated that osmotin prevented Aβ 1-42 -induced apoptosis and neurodegeneration in the Aβ 1-42 -Treated mice. Furthermore, osmotin attenuated Aβ 1-42 -induced neurotoxicity in vitro.To our knowledge, this study is the first to investigate the neuroprotective effect of a novel osmotin against Aβ 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.