Amyloid beta peptide induces cytoplasmic accumulation of amyloid protein precursor via tau protein kinase I/glycogen synthase kinase-3 beta in rat hippocampal neurons.
Exogenous application of synthetic amyloid beta protein (A beta) is known to induce neurotoxic effects in rat hippocampal culture. We report here that A beta (25-35) induces accumulation of amyloid precursor protein (APP) derivatives in the cytoplasm of neurons. At the same time, the level of the secreted form of APP released into the culture medium decreases. Tau protein kinase I/glycogen synthase kinase-3 beta (TPK I/GSK-3 beta) antisense oligonucleotide blocked APP accumulation and prevented neuronal death. These results provide evidence that APP accumulation after A beta treatment is regulated by TPK I/GSK-3 beta. A beta neurotoxicity is probably mediated via phosphorylation of tau by TPK I/GSK-3 beta, resulting in an impairment of axonal transport, and cytoplasmic accumulation of APP.
Takashima
A
A
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Yamaguchi
H
H
Noguchi
K
K
Michel
G
G
Ishiguro
K
K
Sato
K
K
Hoshino
T
T
Hoshi
M
M
Imahori
K
K
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015151:Immunoblotting; D009411:Nerve Endings / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase