Linked Life Data

16248658

Source:http://linkedlifedata.com/resource/pubmed/id/16248658

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2005-10-26
pubmed:abstractText
Amyloid fibrils mainly consist of 40-mer and 42-mer peptides (Abeta40, Abeta42). Abeta42 is believed to play a crucial role in the pathogenesis of Alzheimer's disease because its aggregative ability and neurotoxicity are considerably greater than those of Abeta40. The neurotoxicity of Abeta peptides involving the generation of free radicals is closely related to the S-oxidized radical cation of Met-35. However, the cation's origin and mechanism of stabilization remain unclear. Recently, structural models of fibrillar Abeta42 and Abeta40 based on systematic proline replacement have been proposed by our group [Morimoto, A.; et al. J. Biol. Chem. 2004, 279, 52781] and Wetzel's group [Williams, A. D.; et al. J. Mol. Biol. 2004, 335, 833], respectively. A major difference between these models is that our model of Abeta42 has a C-terminal beta-sheet region. Our biophysical study on Abeta42 using electron spin resonance (ESR) suggests that the S-oxidized radical cation of Met-35 could be generated by the reduction of the tyrosyl radical at Tyr-10 through a turn structure at positions 22 and 23, and stabilized by a C-terminal carboxylate anion through an intramolecular beta-sheet at positions 35-37 and 40-42 to form a C-terminal core that would lead to aggregation. A time-course analysis of the generation of radicals using ESR suggests that stabilization of the radicals by aggregation might be a main reason for the long-lasting oxidative stress of Abeta42. In contrast, the S-oxidized radical cation of Abeta40 is too short-lived to induce potent neurotoxicity because no such stabilization of radicals occurs in Abeta40.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15168-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Formation and stabilization model of the 42-mer Abeta radical: implications for the long-lasting oxidative stress in Alzheimer's disease.
pubmed:affiliation
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't