Linked Life Data

9790168

Source:http://linkedlifedata.com/resource/pubmed/id/9790168

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-11-10
pubmed:abstractText
Chronic inflammatory reactions in the brain appear to be one of the primary etiological factors in the pathogenesis of Alzheimer's disease (AD). This is supported by the fact that the secretory products of inflammatory reactions, which include cytokines, complement proteins, adhesion molecules, and free radicals, are neurotoxic. We have recently reported that prostaglandins (PGs), which are also released during inflammatory reactions, cause rapid degenerative changes in differentiated murine neuroblastoma cells (NB) in culture. PGA1 is more effective than PGE1. Similar observations were made in a primary culture of fetal rat hippocampal cells. Epidemiological and clinical studies on AD also support the involvement of PGs in neuronal degeneration. Thus, we propose a hypothesis that PGs are one of the major extracellular signals that initiate neuronal degeneration, which is mediated by intracellular signals such as the beta-amyloid peptide (Abeta) and ubiquitin, since the levels of these proteins are increased by PG treatment. We further suggest that adenosine 3', 5'-cyclic monophosphate (cAMP) is one of the factors that regulate the levels of both Abeta and ubiquitin in NB cells. Increases in the level of Abeta in NB cells following an elevation of intracellular cAMP levels appear to be due to an increase in the rate of processing of the amyloid precursor protein (APP) rather than an increase in the expression of APP. The mechanisms underlying Abeta-induced neuronal degeneration have been under intense investigation, and several mechanisms of action have been proposed. We postulate that PG-induced elevation of Abeta may lead to an increased binding of Abeta to the 20S proteasome, resulting in a reduction of 20S proteasome-mediated degradation of ubiquitin-conjugated proteins. This is predicted to lead to an increase in an accumulation of abnormal proteins, which ultimately contribute to neuronal degeneration and death. Based on our hypothesis and on studies published by others, we propose that a combination of nonsteroidal anti-inflammatory drugs, which inhibit the synthesis of PGs, and antioxidant vitamins, which quench free radicals and both of which have been recently reported to be of some value in AD treatment when used-individually, may be much more effective in the prevention and treatment of AD than the individual agents alone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0037-9727
pubmed:author
pubmed:issnType
Print
pubmed:volume
219
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-5
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Prostaglandins as putative neurotoxins in Alzheimer's disease.
pubmed:affiliation
Center for Vitamins and Cancer Research, Department of Radiology, University of Colorado Health Sciences Center, School of Medicine, Denver 80262-0228, USA. Kedar.Prasad@UCHSC.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review