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Swedish amyloid precursor protein mutation increases cell cycle‐related proteins in vitro and in vivo
Author(s) -
Ahn KwangWoo,
Joo Yuyoung,
Choi Yoori,
Kim Minji,
Lee Sang Hyoung,
Cha SeokHo,
Suh YooHun,
Kim HyeSun
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21690
Subject(s) - gsk 3 , amyloid precursor protein , cyclin d1 , neurodegeneration , microbiology and biotechnology , biology , cell cycle , gsk3b , kinase , cyclin , alzheimer's disease , cell , medicine , biochemistry , disease
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‐3β 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‐3β 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. © 2008 Wiley‐Liss, Inc.