title: Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT.
abstract: Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin (Htt). Reduced AKT phosphorylation and inhibited AKT activity have been shown to be involved in mutant Htt (mHtt)-induced cell death. Lycium barbarum polysaccharide (LBP), the main bioactive component of Lycium barbarum, reportedly has neuroprotective roles in neural injuries, including neurodegenerative diseases. Here, we report that treatment with LBP can increased the viability of HEK293 cells that stably expressed mHtt containing 160 glutamine repeats and significantly improved motor behavior and life span in HD-transgenic mice. Furthermore, we found that in LBP-treated HEK293 cells expressing mHtt, mHtt levels were reduced and the phosphorylation of AKT at Ser473 (p-AKT-Ser473) was significantly increased. We also found that treatment with LBP increased p-AKT-Ser473 and decreased mHtt in the cortex, hippocampus and striatum in HD-transgenic mice. The level of phosphorylation of p-GSK3β-Ser9 remained unchanged in both cultured cells and HD-transgenic mice. Our findings suggest that LBP alleviates the cytotoxicity of mHtt by activating AKT and reducing mHtt levels, indicating that LBP may be potentially useful for treating HD.
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; Institute for Brain Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Weixi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; Institute for Brain Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: heli@mails.tjmu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics*; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D016019:Survival Analysis; D014162:Transfection
chemical_list: D002867:Chromones; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009025:Morpholines; C500223:lycium barbarum polysaccharide; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3
keywords: AKT; Huntington's disease; Lycium barbarum polysaccharide; Mutant huntingtin