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Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo

Cited 23 time in Web of Science Cited 22 time in Scopus
Authors
Ahn, Kwang-Woo; Joo, Yuyoung; Choi, Yoori; Kim, Minji; Lee, Sang Hyoung; Cha, Seok-Ho; Suh, Yoo-Hun; Kim, Hye-Sun
Issue Date
2008-04-29
Publisher
Wiley-Blackwell
Citation
J Neurosci Res. 86(11):2476-2487
Keywords
Alzheimer Disease/genetics/physiopathologyAmyloid beta-Protein Precursor/*geneticsAnimalsBlotting, WesternBrain/*metabolism/physiopathologyCell Cycle/physiologyCyclin B/*biosynthesis/drug effectsCyclin D1/*biosynthesis/drug effectsEnzyme Inhibitors/pharmacologyHumansImmunohistochemistryImmunoprecipitationMiceMice, TransgenicMutationNeurons/drug effects/*metabolismPC12 CellsRatsReverse Transcriptase Polymerase Chain ReactionUp-Regulation
Abstract
Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)-differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase-3beta inhibitor) down-regulated cyclin B1 induced by Swe-APP expression but up-regulated cyclin D1 expression induced by Swe-APP, suggesting that glycogen synthase kinase-3beta activity is involved in these expression changes of cyclins D1 and B1. Swe-APP, which is a prevailing cause of familial Alzheimer's disease, is well known to increase amyloid beta peptide production both in vitro and in vivo, but the underlying molecular means whereby it leads to the pathogenesis of AD remains unknown. The finding that cyclin D1 and B1 expressions were up-regulated by Swe-APP in in vitro cultured cells was substantiated in the brain tissues of Tg2576 mice, which harbor the Swe-APP mutation. These results suggest that some disturbances in cell cycle regulation may be involved in Swe-APP or AICD-induced neurodegeneration and that these contribute to the pathogenesis of AD.
ISSN
1097-4547 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18438935

http://hdl.handle.net/10371/68351
DOI
https://doi.org/10.1002/jnr.21690
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College of Medicine/School of Medicine (의과대학/대학원)Neurosurgery (신경외과학전공)Journal Papers (저널논문_신경외과학전공)
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