title: FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder in which neuroinflammation plays an important role. FLZ is a novel synthetic derivative of natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective effects on AD models and showed strong anti-inflammatory property in Parkinson's disease models. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property is still not fully elucidated. In this study, we aimed to investigate the ability of FLZ in modulating inflammation. The results showed that FLZ significantly improved memory deficits and alleviated neuronal damage as well as neuronal loss in the hippocampus of mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic studies revealed that the neuroprotective effects of FLZ were due to the suppression of neuroinflammation induced by LPS, as indicated by inactivation of astrocytes and microglia, reduced production of tumor necrosis factor-α, interleukin-1β, and nitric oxide, as well as decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of FLZ on AD were further supported by the finding that FLZ attenuated β-amyloid production through inhibiting β-amyloid precursor protein cleaving enzyme 1 expression. These results suggested that anti-inflammatory agent could be useful for the treatment of AD.
authors.affiliation: a State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Wu
authors.forename: Xiu-Qi
authors.initials: XQ
authors.lastname: Bao
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Pang
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides; D000818:Animals; D044482:Benzeneacetamides / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D006624:Hippocampus / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044482:Benzeneacetamides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; C084439:squamosamide; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Alzheimer's disease; FLZ; lipopolysaccharide; neuroinflammation; β-amyloid