Urso-, Glycoursodeoxycholic and Tauroursodeoxycholic Acids: From Basic Research to Clinical Applications in CNS Disorders
- Pp. 293-325 (33)Dora Brites
Tauroursodeoxycholic acid and glycoursodeoxycholic acid are the conjugates of ursodeoxycholic acid, which is largely used in the treatment of hepatobiliary diseases due to its detergent properties. These bile acids exist only in minor quantities in the normal human body. Ursodeoxycholic acid was approved by U.S. Food and Drug Administration (FDA) for cholesterol gallstone dissolution, and as a cytoprotective agent in primary biliary cirrhosis. Orally administered ursodeoxycholic acid is later conjugated with taurine and glycine in the liver and originates the conjugated species that have fewer side effects than the counterpart free species. Because glycoursodeoxycholic acid may represent more than 50% of total bile acids, and tauroursodeoxycholic usually less than 10%, we consider glycoursodeoxycholic acid as the one having the highest clinical relevance in people taking ursodeoxycholic acid. However, its mechanisms of action have been less explored than the free and the taurine conjugated species. In this overview, the biological properties of glycoursodeoxycholic acid are highlighted and their mechanisms of action compared with ursodeoxycholic acid and tauroursodeoxycholic acid. Recent studies have demonstrated that such bile acids have unexpected efficacy in the treatment of certain neurodegenerative diseases, opening up the range of opportunities for their therapeutic use. Therefore, we additionally summarize current knowledge on the potential applications of such bile acids in the prevention and recovery of diseases associated to central nervous system (CNS) dysfunction and pathology. Forthcoming studies will hopefully better elucidate the benefits of glycoursodeoxycholic acid over those of ursodeoxycholic acid and tauroursodeoxycholic acid for the treatment of age-associated neurodegenerative diseases, a major public health issue and a challenge to the health care system.