title: 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 (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.
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Tahir
authors.initials: T
authors.lastname: Ali
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Gwang Ho
authors.initials: GH
authors.lastname: Yoon
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Shahid Ali
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001522:Behavior, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010940:Plant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010940:Plant Proteins; D016875:tau Proteins; C073139:osmotin protein, Nicotiana tabacum; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D016282:Aspartic Acid Endopeptidases