Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.
Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Haroon
H
Badshah
Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Tahir
T
Ali
Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Myeong Ok
MO
Kim
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers; D002460:Cell Line; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000523:psychology*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000523:psychology; D010937:Plant Growth Regulators / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D015415:Biomarkers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010937:Plant Growth Regulators; D051197:Toll-Like Receptor 4