title: Involvement of GSK3 and PP2A in ginsenoside Rb1's attenuation of aluminum-induced tau hyperphosphorylation.
abstract: Environmental agent aluminum, a well-known neurotoxin, has been proposed to play a role in the development of Alzheimer's disease (AD), and produced clinical and pathological features which were strikingly similar to those seen in AD brain, such as neurofibrillary tangles. Ginsenoside Rb1, highly abundant active component of ginseng, has been demonstrated to be neuroprotective against various neurotoxins. In this study we investigated the effect of Rb1 on aluminum-induced tau hyperphosphorylation in ICR mice. Mice were exposed to aluminum chloride (200 mg/kg/day) for 6 months followed by a post treatment of Rb1 (20 mg/kg/day) for another 4 months. Aluminum exposure induced the cognitive ability by Morris water maze, and upregulated the tau phosphorylation level at Ser396 accompanied by increasing p-GSK and decreasing PP2A level in motor, sensory cortex and hippocampal formation. Post treatment of Rb1 significantly improved the learning and memory and reduced the tau phosphorylation by reversing the p-GSK3 and PP2A level. Our results indicate that ginsenoside Rb1 protected mice against Al-induced toxicity. The possible mechanism may be its role in preventing tau hyperphosphorylation by regulating p-GSK3 and PP2A level, which implicate Rb1 as the potential preventive drug candidate for AD and other tau pathology-related neuronal degenerative diseases.
authors.affiliation: Department of Human Anatomy, College of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Hai-hua
authors.initials: HH
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Di
authors.forename: Wen-su
authors.initials: WS
authors.lastname: Liu
authors.forename: Hui-li
authors.initials: HL
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Lai
authors.forename: Yong-li
authors.initials: YL
authors.lastname: Lü
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D036145:Ginsenosides; D018696:Neuroprotective Agents; D016875:tau Proteins; D000077410:Aluminum Chloride; C442759:ginsenoside Rb1; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2