Linked Life Data

16605241

Source:http://linkedlifedata.com/resource/pubmed/id/16605241

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2006-4-11
pubmed:abstractText
Gaining insight into the mechanism of amyloid fibril formation, the hallmark of multiple degenerative syndromes of unrelated origin, and exploring novel directions of inhibition are crucial for preventing disease development. Specific interactions between aromatic moieties were suggested to have a key role in the recognition and self-assembly processes leading to the formation of amyloid fibrils by several amyloidogenic polypeptides, including the beta-amyloid polypeptide associated with Alzheimer's disease. Our finding of the high-affinity molecular recognition and intense amyloidogenic potential of tryptophan-containing peptide fragments led to the hypothesis that screening for indole derivatives might lead to the identification of potential inhibitors of amyloid formation. Such inhibitors could mediate specific recognition processes without allowing further growth of the well-ordered amyloid chain. Using fluorescence spectroscopy, atomic force microscopy, and electron microscopy to screen 29 indole derivatives, we identified three potent inhibitors: indole-3-carbinol (I3C), 3-hydroxyindole (3HI), and 4-hydroxyindole (4HI). The latter, a simple low-molecular weight aromatic compound, was the most effective, completely abrogating not only the formation of aggregated structures by Abeta but also the cytotoxic activity of aggregated Abeta toward cultured cells. The results of this study provide further experimental support for the paradigm of amyloid inhibition by heteroaromatic interaction and point to indole derivatives as a simple molecular platform for the development of novel fibrillization inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4727-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Inhibition of amyloid fibril formation and cytotoxicity by hydroxyindole derivatives.
pubmed:affiliation
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't