Linked Life Data

9869322

Source:http://linkedlifedata.com/resource/pubmed/id/9869322

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8-9
pubmed:dateCreated
1999-3-16
pubmed:abstractText
The mismetabolism of amyloid precursor protein (APP), favouring the production of A beta, is considered to be central to the pathogenesis of Alzheimer's disease (AD). However it remains to be established whether the causative factor is the reported toxicity of A beta or reduced production of secretory derivatives of APP which may have trophic or neuroprotective properties. One possible contributory factor to an imbalance in APP metabolism is the impaired cellular energy availability described in AD. The aim of this study was to investigate processing of APP-like proteins following inhibition of oxidative energy metabolism in PC12 cells. Under these conditions, intracellular and secreted APP-like proteins were significantly reduced. Treatment of energy perturbed cells with the lysosomotropic agent chloroquine restored intracellular concentrations of APP-like proteins to the control range, while the secretion was completely restored by activation of protein kinase C. These findings raise the possibility that energy related metabolic stress may lead to altered metabolism of APP-like proteins favouring a potentially amyloidogenic pathway. Furthermore, the observation that activation of PKC is able to overcome this potentially pathogenic process has important implications for treatment of AD with the current generation of cholinomimetic drugs, suggesting that such drugs may slow disease progression as well as improve cognitive dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-9564
pubmed:author
pubmed:issnType
Print
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
839-53
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The effects of perturbed energy metabolism on the processing of amyloid precursor protein in PC12 cells.
pubmed:affiliation
Dementia Research Laboratory, Biochemical Neuropharmacology Group, UMDS, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't