What do people think of UDCA and Tauroursodeoxycholic Acid for neuroprotection? anyone tried them?
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Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a US Food and Drug Administration-approved hydrophilic bile acid for the treatment of certain cholestatic liver diseases. There is a growing body of research on the mechanism(s) of TUDCA and its potential therapeutic effect on a wide variety of non-liver diseases. Both UDCA and TUDCA are potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response (UPR). Several studies have demonstrated that TUDCA serves as an anti-apoptotic agent for a number of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. In addition, TUDCA plays an important role in protecting against cell death in certain retinal disorders, such as retinitis pigmentosa. It has been shown to reduce ER stress associated with elevated glucose levels in diabetes by inhibiting caspase activation, up-regulating the UPR, and inhibiting reactive oxygen species. Obesity, stroke, acute myocardial infarction, spinal cord injury, and a long list of acute and chronic non-liver diseases associated with apoptosis are all potential therapeutic targets for T/UDCA. A growing number of pre-clinical and clinical studies underscore the potential benefit of this simple, naturally occurring bile acid, which has been used in Chinese medicine for more than 3000 years.
To further characterize mitochondrial dysfunction in LRRK2G2019S mutant Parkinson disease (PD) patient tissue (M-LRRK2G2019S), determine whether ursodeoxycholic acid (UDCA) also exerts a beneficial effect on mitochondrial dysfunction in nonmanifesting LRRK2G2019Smutation carriers (NM-LRRK2G2019S), and assess UDCA for its beneficial effect on neuronal dysfunction in vivo.
METHODS:Intracellular adenosine 5'-triphosphate (ATP) levels, oxygen consumption, and activity of the individual complexes of the mitochondrial respiratory chain as well as mitochondrial morphology were measured in M-LRRK2G2019S, NM-LRRK2G2019S, and controls. UDCA was assessed for its rescue effect on intracellular ATP levels in NM-LRRK2G2019S and in a LRRK2 transgenic fly model with dopaminergic expression of LRRK2G2019S.
RESULTS:Crucial parameters of mitochondrial function were similarly reduced in both M-LRRK2G2019S and NM-LRRK2G2019S with a specific decrease in respiratory chain complex IV activity. Mitochondrial dysfunction precedes changes in mitochondrial morphology but is normalized after siRNA-mediated knockdown of LRRK2. UDCA improved mitochondrial function in NM-LRRK2G2019 and rescued the loss of visual function in LRRK2G2019S flies.
CONCLUSION:There is clear preclinical impairment of mitochondrial function in NM-LRRK2G2019S that is distinct from the mitochondrial impairment observed in parkin-related PD. The beneficial effect of UDCA on mitochondrial function in both NM-LRRK2G2019S and M-LRRK2G2019S as well as on the function of dopaminergic neurons expressing LRRK2G2019S suggests that UDCA is a promising drug for future neuroprotective trials.
© 2015 American Academy of Neurology.