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.
Keywords: Bile acids, Bile acid physiology, Blood-brain barrier, Cytoprotection,
Endothelial cells, Hepatobiliary disorders, Neurodegenerative diseases,
Neurogenesis.
