Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-4-9
pubmed:abstractText
A number of mechanisms have been proposed to contribute to the selective neuronal cell loss observed during Alzheimer disease (AD). These include the formation and accumulation of amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles (NFTs), and inflammatory processes mediated by astrocytes and microglia. Neuronal responses to such insults in AD brain include increased protein levels and immunoreactivity for kinases known to regulate cell cycle progression. One down-stream target of these cell cycle regulatory proteins, the Retinoblastoma susceptibility gene product (pRb), has been shown to exhibit altered expression patterns in AD. Furthermore, in vitro studies have implicated pRb and one of the transcription factors it regulates, E2F1, in Abeta-induced cell death. To further explore the role of these proteins in AD, we examined the distribution of the E2F1 transcription factor and the hyperphosphorylated form of pRb (ppRb), which is unable to bind and regulate E2F activity, in the cortex of patients with AD and in non-demented controls. We observed increased ppRb and E2FI immunoreactivity in AD brain, with ppRb predominately located in the nucleus and E2F1 in the cytoplasm. Although neither of these proteins significantly co-localized with NFTs, both ppRb and E2F1 were found in cells surrounding a subset of Abeta-containing plaques. These results support a role for G1 to S phase cell cycle regulators in AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
358-67
pubmed:dateRevised
2011-6-9
pubmed:meshHeading
pubmed-meshheading:11939591-Aged, pubmed-meshheading:11939591-Aged, 80 and over, pubmed-meshheading:11939591-Alzheimer Disease, pubmed-meshheading:11939591-Cell Cycle, pubmed-meshheading:11939591-Cell Cycle Proteins, pubmed-meshheading:11939591-Cerebral Cortex, pubmed-meshheading:11939591-DNA-Binding Proteins, pubmed-meshheading:11939591-E2F Transcription Factors, pubmed-meshheading:11939591-E2F1 Transcription Factor, pubmed-meshheading:11939591-Female, pubmed-meshheading:11939591-Humans, pubmed-meshheading:11939591-Immunohistochemistry, pubmed-meshheading:11939591-Male, pubmed-meshheading:11939591-Middle Aged, pubmed-meshheading:11939591-Neurons, pubmed-meshheading:11939591-Phosphorylation, pubmed-meshheading:11939591-Retinoblastoma Protein, pubmed-meshheading:11939591-Transcription Factors, pubmed-meshheading:11939591-tau Proteins
pubmed:year
2002
pubmed:articleTitle
Altered distribution of cell cycle transcriptional regulators during Alzheimer disease.
pubmed:affiliation
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't