title: Illite improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer׳s disease through Akt/CREB and GSK-3β phosphorylation in the brain.
abstract: BACKGROUND
  The use of illite in Korean medicine has a long history as a therapeutic agent for various cerebrovascular diseases. According to Dongui Bogam, illite can be used for Qi-tonifying, phlegm dispersing and activation of blood circulation which is an important principle for the treatment of brain-associated diseases.
  
  
  OBJECTIVE
  This study was undertaken to evaluate beneficial effects of illite on the neurodegenerative diseases such as Alzheimer׳s disease (AD).
  
  
  METHODS
  The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed with 1% or 3% of illite for 3 months. Behavioral, immunological and ELISA analyses were used to assess memory impairment with additional measurement of Aβ accumulation and plaque deposition in the brain. Other in vitro studies were performed to examine whether illite inhibits the Aβ-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells.
  
  
  RESULTS
  Illite treatment rescued Aβ-induced neurotoxicity on SH-SY5Y cells, which was dependent on the PI3K/Akt activation. Intake of illite improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice. Illite increased CREB, Akt, and GSK-3β phosphorylation and suppressed tau phosphorylation in the AD-like brains. Moreover, 1% of illite reduced weight gain and suppressed glucose level in the blood.
  
  
  CONCLUSIONS
  The present study suggests that illite has the potential to be a useful adjunct as a therapeutic drug for the treatment of AD.
authors.affiliation: Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea. Electronic address: jsong0304@dongguk.edu.
authors.forename: Songhee
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
authors.forename: Quan Feng
authors.initials: QF
authors.lastname: Liu
authors.affiliation: Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea.
authors.forename: Ha Jin
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW 2795, Australia.
authors.forename: Sok Cheon
authors.initials: SC
authors.lastname: Pak
authors.affiliation: Yong-dong Illite Co., Ltd., 32, Mocdongnamno Gurogu, Seoul, Republic of Korea.
authors.forename: Sudok
authors.initials: S
authors.lastname: Yi
authors.affiliation: Department of Chemisty, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 1-5, Anam Dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea.
authors.forename: Chan-Wha
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea.
authors.forename: Jung-Keug
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Korean Neuropsychiatry, Dongguk University Bundang Oriental Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Geun Woo
authors.initials: GW
authors.lastname: Kim
authors.affiliation: Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea. Electronic address: koobs@dongguk.ac.kr.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Koo
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic; D008903:Minerals / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000188:drug therapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D001786:Blood Glucose; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008903:Minerals; C099089:illite; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Akt; Alzheimer׳s disease; Beta-amyloid; CREB; Illite; Lithium