Linked Life Data

16442744

Source:http://linkedlifedata.com/resource/pubmed/id/16442744

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-2-13
pubmed:abstractText
The post-translational modifications of protein molecules include glycation, which may not only occur enzymatically controlled in N and O position, but also wherever proteins meet reducing sugars non-enzymatically in epsilon position at lysines (non-enzymatic (epsilon) glycation (NEG)). The formation of keto-amines from the amine-sugar compounds (Amadori re-arrangement) and further processing of the largely undigestible Amadori compounds eventually results in insoluble advanced glycation end products (AGEs). The latter can induce or favour disease including mental disorders. Preferential targets of NEG include large cell surface proteins. Ample evidence has been provided that NEG also occurs in the brain where cross-linking of epsilon-glycated proteins, induction of oxidative stress and signalling of AGEs through their specific receptor (RAGE) likely play a role in (brain) ageing and Alzheimer disease (AD). This is underscored by the demonstration of particular interactions between AGE/RAGE and amyloid-beta (Abeta) that favour the aggregation and deposition of Abeta and, perhaps, the formation of Abeta itself. The close relationship between NEG and Abeta, as well as other facts foster the hypothesis that NEG of the large trans-membrane amyloid precursor protein (APP) might be a significant factor in the induction of aberrant APP cleavage with production of Abeta, not only in normal ageing, but also in AD. Blockade of lysine cleavage sites on APP by sugar chains or marker effects induced by NEG akin to ubiquitination of proteins for degradation at lysines could be expected to contribute to altered processing of APP. The hypothesis of epsilon-glycation in APP proposed here and the review of evidences for the significance of NEG in brain ageing and AD are aimed at the stimulation of investigations into the still open question which role NEG plays with respect to APP and its abnormal processing in AD. It can be rendered likely that such research might open new avenues towards decreasing the risk of AD and/or slowing its progression through the prevention of NEG in APP with aberrant APP processing, increased generation of Abeta and the formation of AGEs from epsilon-glycated APP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-9877
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
898-906
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
epsilon-Glycation, APP and Abeta in ageing and Alzheimer disease: a hypothesis.
pubmed:affiliation
Institute of Pathology, Department for Neuropathology, University of Heidelberg, Germany. horst.schmitt@med.uni-heidelberg.de
pubmed:publicationType
Journal Article