Premium
Modulation of amyloid‐β aggregation and toxicity by inosose stereoisomers
Author(s) -
Nitz Mark,
Fenili Daniela,
Darabie Audrey A.,
Wu Ling,
Cousins Julian E.,
McLaurin JoAnne
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06321.x
Subject(s) - neurodegeneration , chemistry , inositol , amyloid (mycology) , fibrillogenesis , biochemistry , in vitro , alzheimer's disease , in vivo , toxicity , pharmacology , biophysics , biology , medicine , receptor , disease , organic chemistry , inorganic chemistry , microbiology and biotechnology
Amyloid‐β (Aβ) aggregation and amyloid formation are key pathological features of Alzheimer’s disease, and are considered to be two of the major contributing factors to neurodegeneration and dementia. Identification of small molecule inhibitors that are orally available, have low toxicity and high central nervous system bioavailability is one approach to the potential development of a disease‐modifying treatment for Alzheimer’s disease. We have previously identified inositol stereoisomers as exhibiting stereospecific inhibition of Aβ aggregation and toxicity in vitro and in vivo . We report here the effects of inosose versus inositol stereoisomers on Aβ fibrillogenesis as determined using CD and fluorescence spectroscopy and negative‐stain electron microscopy. The inososes differ from inositols by the oxidation of one of the hydroxyl groups to a ketone. These molecules help in the further elucidation of the structure–activity relationships of inositol–Aβ interactions and identify both allo ‐inositol and epi ‐2‐inosose as in vitro inhibitors of Aβ aggregation.