title: Decreasing oxidative stress and neuroinflammation with a multifunctional peptide rescues memory deficits in mice with Alzheimer disease.
abstract: Alzheimer disease (AD) is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, and memory loss. Aggregated amyloid-β (Aβ), oxidative stress, and inflammation have pivotal roles in the pathogenesis of AD. Therefore, the inhibition of Aβ-induced neurotoxicity, oxidative stress, and inflammation is a potential therapeutic strategy for the treatment of AD. In this study, a heptapeptide, isolated from a Ph.D.-C7C library by phage display, attenuated Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells and reduced Aβ42-induced oxidative stress by decreasing the production of reactive oxygen species and glutathione disulfide. As a result, glutathione level increased and superoxide dismutase and glutathione peroxidase activities were enhanced in vitro and in vivo. This peptide also suppressed the inflammatory response by decreasing the release of proinflammatory cytokines, such as tumor necrosis factor α and interleukin 1β, in microglia and by reducing microgliosis and astrogliosis in AD transgenic mice. This peptide was intracerebroventricularly administered to APPswe/PS1dE9 transgenic mice. We found that this peptide significantly improved spatial memory and reduced the amyloid plaque burden and soluble and insoluble Aβ levels. Our findings suggest that this multifunctional peptide has therapeutic potential for an Aβ-targeted treatment of AD.
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors: Wei-wei
authors: WW
authors: Zhou
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors: Shuai
authors: S
authors: Lu
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; School of Life Science, Ningxia University, Yinchuan 750021, China.
authors: Ya-jing
authors: YJ
authors: Su
authors: School of Life Science, Ningxia University, Yinchuan 750021, China.
authors: Di
authors: D
authors: Xue
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors: Xiao-lin
authors: XL
authors: Yu
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors: Shao-wei
authors: SW
authors: Wang
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors: He
authors: H
authors: Zhang
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; School of Life Science, Ningxia University, Yinchuan 750021, China.
authors: Peng-xin
authors: PX
authors: Xu
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: xxxie@home.ipe.ac.cn.
authors: Xi-xiu
authors: XX
authors: Xie
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: rtliu@home.ipe.ac.cn.
authors: Rui-tian
authors: RT
authors: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019151:Peptide Library; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D009842:Oligopeptides; D010446:Peptide Fragments; D019151:Peptide Library; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C000598110:seryl-methionyl-seryl-alanyl-arginyl-glutaminyl-leucine; D019803:Glutathione Disulfide
keywords: Alzheimer disease; Free radicals; Inflammation; Oxidative stress; Peptide; β-Amyloid