Linked Life Data

10412022

Source:http://linkedlifedata.com/resource/pubmed/id/10412022

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-9-8
pubmed:abstractText
In Alzheimer's disease (AD) synapses degenerate and neurons die in brain regions involved in learning and memory processes. Although the cellular and molecular mechanisms underlying the neurodegenerative process in AD are unclear, increasing evidence suggests roles for amyloid beta-peptide (Abeta) and biochemical cascades associated with a form of programmed cell death called apoptosis. Cysteine proteases of the caspase family are activated in neurons undergoing apoptosis and apparently play a major role in the cell death process by cleaving yet-to-be-identified substrates. We now report that caspase activity is increased in brain tissue and neurons from AD patients, and in cultured hippocampal neurons undergoing apoptosis after exposure to amyloid beta-peptide (Abeta). Western blot analyses using antibodies against different subunits of 2-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) types of ionotropic glutamate receptors indicate that AMPA receptor subunits (GluR1, GluR2/3, and GluR4), but not NMDA receptor subunits (NR1 and NR2A), are proteolytically cleaved after exposure of hippocampal neurons to apoptotic insults, including Abeta, and that the caspase inhibitor zVAD-fmk suppresses such cleavage. Western blot analysis of brain tissue from AD patients and age-matched controls revealed evidence for increased proteolysis of AMPA receptor subunits in AD. Our data suggest roles for caspase-mediated cleavage of AMPA receptor subunits in modifying neuronal responsivity to glutamate and in the neurodegenerative process in AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Evidence for caspase-mediated cleavage of AMPA receptor subunits in neuronal apoptosis and Alzheimer's disease.
pubmed:affiliation
Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536-0230, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.