摘要：The pathological hallmarks of Alzheimer’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 (15 μg/g, intraperitoneally, 4 hr) at 3 and 40 days post-intracerebroventricular injection of Aβ1-42 significantly ameliorated Aβ1-42-induced memory impairment in mice. These results revealed that osmotin reverses Aβ1-42 injection-induced synaptic deficits, Aβ accumulation and BACE-1 expression. Treatment with osmotin also alleviated the Aβ1-42-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 Aβ1-42-induced apoptosis and neurodegeneration in the Aβ1-42-treated mice. Furthermore, osmotin attenuated Aβ1-42-induced neurotoxicity in vitro . To our knowledge, this study is the first to investigate the neuroprotective effect of a novel osmotin against Aβ1-42-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.
