Up-regulation of calsyntenin-3 by β-amyloid increases vulnerability of cortical neurons.
β-Amyloid (Aβ) may play an important role in the pathogenesis of Alzheimer's disease. However, a causal relationship between Aβ oligomers and layer-specific neurodegeneration has not been clarified. Here we show up-regulation of calsyntenin (Cst)-3 in cultured neurons treated with Aβ oligomers and in Tg2576 mice. Cst-3 is distributed in large neurons in layers 2-3 and 5 of the cerebral cortex, and accumulated in dystrophic neurites surrounding Aβ-plaques. Overexpression of Cst-3 accelerates neuronal death. These results indicate that up-regulation of Cst-3 in cortical neurons in layers 2-3 and 5 by Aβ oligomers may lead to increase in vulnerability of neurons.
Molecular Neurobiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 57uchida@tmig.or.jp
Yoko
Y
Uchida
Shun-ichirou
S
Nakano
Fujiya
F
Gomi
Hiroshi
H
Takahashi
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004622:Embryo, Mammalian; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C472551:CLSTN2 protein, human; C472553:CLSTN3 protein, human; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C075222:amyloid beta-protein (1-42)