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?) 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 ?g/g, intraperitoneally, 4 hr) at 3 and 40 days post-intracerebroventricular injection of A?1-42 significantly ameliorated A?1-42-induced memory impairment in mice. These results revealed that osmotin reverses A?1-42 injection-induced synaptic deficits, A? accumulation and BACE-1 expression. Treatment with osmotin also alleviated the A?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? (serine 9). Moreover, our western blots and immunohistochemical results indicated that osmotin prevented A?1-42-induced apoptosis and neurodegeneration in the A?1-42-treated mice. Furthermore, osmotin attenuated A?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?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.

SUBMITTER: Ali T 

PROVIDER: S-EPMC4484370 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other