A new face for old antibiotics: tetracyclines in treatment of amyloidoses.

Abstract

The use of tetracyclines has declined because of the appearance of resistant bacterial strains. However, the indications of nonantimicrobial activities of these drugs have considerably raised interest and triggered clinical trials for a number of different pathologies. About 10 years ago we first reported that tetracyclines inhibited the aggregation of prion protein fragments and Alzheimer's β peptides, destabilizing their aggregates and promoting their degradation by proteases. On the basis of these observations, the antiamyloidogenic effects of tetracyclines on a variety of amyloidogenic proteins were studied and confirmed by independent research groups. In this review we comment on the data available on their antiamyloidogenic activity in preclinical and clinical studies. We also put forward that the beneficial effects of these drugs are a result of a peculiar pleiotropic action, comprising their interaction with oligomers and disruption of fibrils, as well as their antioxidant, anti-inflammatory, antiapoptotic, and matrix metalloproteinase inhibitory activities.

• Authors: Tatiana Stoilova, Laura Colombo, Gianluigi Forloni, Fabrizio Tagliavini, Mario Salmona
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 56 Issue 15 Pg. 5987-6006 (Aug 08 2013) ISSN: 1520-4804 [Electronic] United States
• PMID: 23611039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Amyloid
• Amyloidogenic Proteins
• Anti-Bacterial Agents
• Anti-Inflammatory Agents
• Antioxidants
• Matrix Metalloproteinase Inhibitors
• Tetracyclines

Topics

• Amyloid (chemistry, metabolism)
• Amyloidogenic Proteins (chemistry, metabolism)
• Amyloidosis (drug therapy, metabolism, pathology)
• Animals
• Anti-Bacterial Agents (chemistry, therapeutic use)
• Anti-Inflammatory Agents (chemistry, therapeutic use)
• Antioxidants (chemistry, therapeutic use)
• Apoptosis (drug effects)
• Clinical Trials as Topic
• Drug Administration Schedule
• Humans
• Matrix Metalloproteinase Inhibitors (chemistry, therapeutic use)
• Protein Conformation
• Tetracyclines (chemistry, therapeutic use)