Document Detail

Dihydroxybenzoic acid isomers differentially dissociate soluble biotinyl-Aβ(1-42) oligomers.
MedLine Citation:
PMID:  22129351     Owner:  NLM     Status:  MEDLINE    
Polyphenolic compounds including a number of natural products such as resveratrol, curcumin, catechin derivatives, and nordihydroguaiaretic acid have effects on the assembly of Aβ fibrils and oligomers as well as on fibril morphology. Based on a lead structure obtained from a screen of a small molecule diversity library, simple benzoic acid derivatives distinguished by the number and position of hydroxyls on the aromatic ring displayed different abilities to dissociate preformed biotinyl-Aβ(1-42) oligomers. The 2,3-, 2,5-, and 3,4-dihydroxybenzoic acid (DHBA) isomers were active oligomer dissociators. The remaining DHBA isomers and the monohydroxy and unsubstituted benzoic acids were inactive and did not compete with the active compounds to block oligomer dissociation. None of the compounds blocked oligomer assembly, indicating that they do not interact with monomeric Aβ to shift the oligomer-monomer equilibrium. Dissociating activity was not associated with quinone redox cycling capacity of the compounds. Gallic acid (3,4,5-trihydroxybenzoic acid) stabilized biotinyl-Aβ(1-42) oligomers against intrinsic dissociation and blocked the effects of the active dissociators, independent of the concentration of dissociator. A model for the mechanism of action of the DHBA dissociators proposes that these compounds destabilize oligomer structure promoting progressive monomer dissociation rather than fissioning oligomers into smaller, but still macromolecular, species. Gallic acid blocks dissociation by stabilizing oligomers against this process.
Harry LeVine; Levi Lampe; Lina Abdelmoti; Corinne E Augelli-Szafran
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-08
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-03-08     Revised Date:  2014-05-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  307-15     Citation Subset:  IM    
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MeSH Terms
Alzheimer Disease / metabolism
Amyloid beta-Peptides / antagonists & inhibitors*,  chemistry*,  metabolism
Benzoic Acid / chemistry*
Catechols / chemistry*
Dopamine / analogs & derivatives,  chemistry
Glutaral / chemistry
Peptide Fragments / antagonists & inhibitors*,  chemistry*,  metabolism
Grant Support
Reg. No./Substance:
0/2,3-dihydroxy benzoic acid; 0/Amyloid beta-Peptides; 0/Catechols; 0/Peptide Fragments; 0/amyloid beta-protein (1-42); 37491-68-2/3,4-dihydroxybenzylamine; 65-85-0/Benzoic Acid; T3C89M417N/Glutaral; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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