Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100.
To examine the regulation of amyloid secretion in more detail, Abeta sandwich ELISAs with high sensitivity and specificity were developed. Using this technique, we measured Abeta secreted from COS7 cells transiently transfected with APP C100 in the presence of LiCl, a potent glycogen synthase kinase (GSK)-3beta inhibitor. We found that both Abetax-40 and Abetax-42 secretion were reduced by LiCl treatment in a dose-dependent manner. Diminished amyloid secretion was associated with GSK-3beta activity. These results suggest that GSK-3beta might function as a possible mediator for regulating both amyloid deposition and tau pathology in Alzheimer's disease (AD), and that lithium should be re-evaluated as a candidate reagent for preventing AD pathology.
Sun
X
X
Lab for Alzheimer's Disease, The Brain Science Institute of RIKEN, 2-1 Hirosawa, Wako, 351-0198 Saitama, Japan.
Sato
S
S
Murayama
O
O
Murayama
M
M
Park
J-M
JM
Yamaguchi
H
H
Takashima
A
A
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D018021:Lithium Chloride / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D015534:Trans-Activators; D051176:beta Catenin
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D015534:Trans-Activators; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D051176:beta Catenin; D006006:Glycogen Synthase; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride