Another offering for the X100 list is Alteon (ALT, previously ALTN). They have a candidate, aminoguanidine, in P I trials for diabetic and age-related complications and in preclinical programs for other indications. This is an advanced glycation endproduct (AGE) inhibitor. There are articles in several journals that discuss a possible connection between AGEs and oxidative stress and cytotoxicity, including mention of dementia, diabetic nerve damage and atherogenesis. A Medline search on "advanced glycation endproduct "got over 70 hits, including the gem below. That one makes me want to celebrate with a cool brew. But before that, there is also evidence that existing AGEs can be eliminated (http://www.siliconinvestor.com/readmsg.aspx?msgid=13202915), which is worth another cool one.
Jason
Title
Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol.
Author
Al Abed Y; Mitsuhashi T; Li H; Lawson JA; FitzGerald GA; Founds H; Donnelly T; Cerami A; Ulrich P; Bucala R
Address
Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 10030, USA.
Source
Proc Natl Acad Sci U S A, 1999 Mar, 96:5, 2385-90
Abstract
Epidemiological studies suggest that there is a beneficial effect of moderate ethanol consumption on the incidence of cardiovascular disease. Ethanol is metabolized to acetaldehyde, a two-carbon carbonyl compound that can react with nucleophiles to form covalent addition products. We have identified a biochemical modification produced by the reaction of acetaldehyde with protein-bound Amadori products. Amadori products typically arise from the nonenzymatic addition of reducing sugars (such as glucose) to protein amino groups and are the precursors to irreversibly bound, crosslinking moieties called advanced glycation endproducts, or AGEs. AGEs accumulate over time on plasma lipoproteins and vascular wall components and play an important role in the development of diabetes- and age-related cardiovascular disease. The attachment of acetaldehyde to a model Amadori product produces a chemically stabilized complex that cannot rearrange and progress to AGE formation. We tested the role of this reaction in preventing AGE formation in vivo by administering ethanol to diabetic rats, which normally exhibit increased AGE formation and high circulating levels of the hemoglobin Amadori product, HbA1c, and the hemoglobin AGE product, Hb-AGE. In this model study, diabetic rats fed an ethanol diet for 4 weeks showed a 52% decrease in Hb-AGE when compared with diabetic controls (P < 0.001). Circulating levels of HbA1c were unaffected by ethanol, pointing to the specificity of the acetaldehyde reaction for the post-Amadori, advanced glycation process. These data suggest a possible mechanism for the so-called "French paradox," (the cardioprotection conferred by moderate ethanol ingestion) and may offer new strategies for inhibiting advanced glycation.
Language of Publication
English
Unique Identifier
99162614
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