Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-7-28
pubmed:abstractText
Herein we demonstrate that PC12 cells, which overexpress human wild-type amyloid-beta precursor protein (AbetaPPwt) or AbetaPP bearing double Swedish mutation (AbetaPPsw), reveal phenotype characteristic for Alzheimer's disease (AD). The examination of cell ultrastructure showed the presence of peptide aggregates within the cells, activation of endosomal-lysosomal system and extensive exocytosis. Furthermore, the autophagy induction was also characteristic hallmark of amyloid-beta-induced cytotoxicity. Morphological changes were positively correlated with the extent of phosphorylated glycogen synthase kinase-3beta (phospho-Tyr(216)-GSK-3beta, GSK-3beta-P(Y216)). The activity of GSK-3beta is believed to cause tau protein hyper-phosphorylation, increased amyloid-beta production and local plaque-associated microglial-mediated inflammatory responses. All of them are symptomatic for AD. In our studies, the highly significant Y216 phosphorylation and over-expression of total GSK-3beta were observed in AbetaPPsw-transfected PC12 cells. In addition, the immuocytochemical analysis showed co-localization of GSK-3beta-P(Y216) and amyloid-beta deposits. Thus, our data support a functional role of GSK-3beta in AbetaPP processing, further implicating this kinase in the amyloid-beta-dependent pathogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1872-9711
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
581-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Alzheimer's disease genetic mutation evokes ultrastructural alterations: correlation to an intracellular Abeta deposition and the level of GSK-3beta-P(Y216) phosphorylated form.
pubmed:affiliation
Department of Cell Ultrastructure, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. bepaj@wp.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't