A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington's disease

There is currently no effective treatment for Huntington's disease (HD), a progressive, fatal, neurodegenerative disorder characterized by motor and c ognitive deterioration. It is well established that HD is associated with p erturbation of mitochondrial energy metabolism. Tauroursodeoxycholic acid ( TUDCA), a naturally occurring bile acid, can stabilize the mitochondrial me mbrane, inhibit the mitochondrial permeability transition, decrease free ra dical formation, and derail apoptotic pathways. Here we report that TUDCA s ignificantly reduced 3-nitropropionic acid (3NP)-mediated striatal neuronal cell death in cell culture. In addition, rats treated with TUDCA exhibited an 80% reduction in apoptosis and in lesion volumes associated with 3-NP a dministration. Moreover, rats which received a combination of TUDCA + 3-NP exhibited sensorimotor and cognitive task performance that was indistinguis hable from that of controls, and this effect persisted at least 6 months. B ile acids have traditionally been used as therapeutic agents for certain li ver diseases. This is the first demonstration, however, that a bile acid ca n be delivered to the brain and function as a neuroprotectant and thus may offer potential therapeutic benefit in the treatment of certain neurodegene rative diseases. (C) 2001 Academic Press.