Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-7-30
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-4547
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2476-87
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18438935-Alzheimer Disease, pubmed-meshheading:18438935-Amyloid beta-Protein Precursor, pubmed-meshheading:18438935-Animals, pubmed-meshheading:18438935-Blotting, Western, pubmed-meshheading:18438935-Brain, pubmed-meshheading:18438935-Cell Cycle, pubmed-meshheading:18438935-Cyclin B, pubmed-meshheading:18438935-Cyclin B1, pubmed-meshheading:18438935-Cyclin D1, pubmed-meshheading:18438935-Enzyme Inhibitors, pubmed-meshheading:18438935-Humans, pubmed-meshheading:18438935-Immunohistochemistry, pubmed-meshheading:18438935-Immunoprecipitation, pubmed-meshheading:18438935-Mice, pubmed-meshheading:18438935-Mice, Transgenic, pubmed-meshheading:18438935-Mutation, pubmed-meshheading:18438935-Neurons, pubmed-meshheading:18438935-PC12 Cells, pubmed-meshheading:18438935-Rats, pubmed-meshheading:18438935-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18438935-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo.
pubmed:affiliation
Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't