The effects of ursodeoxycholic acid on Parkinson's disease, a mechanistic review of the recent evidence

Abstract

Parkinson`s disease stands as the second-most widespread neurodegenerative disorder. Parkinson`s disease is relentless in progression and irreversible in nature, for which there is no cure. Therapies are only used to attenuate motor symptoms. As Parkinson`s disease is primarily defined by degeneration of dopaminergic neurons in the substantia nigra, and considering that neuroinflammation and mitochondrial dysfunction in these neurons are key factors contributing to disease progression, alternative therapies should aim to preserve healthy mitochondria. Method. Eligible studies on the effect of Ursodeoxycholic acid (UDCA) on Parkinson`s disease were collected from PubMed, Google Scholar, Scopus, Web of Science and Cochrane library for clinical, in-vivo, and in-vitro studies. Result. UDCA and its taurine conjugate (TUDCA), which are endogenous bile acids, have exhibited neuroprotective potential in various neurological conditions, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, in both animal experimental models and clinical investigations. This is attributed to three significant properties, in addition to their capability to cross the blood-brain barrier. First, their anti-inflammatory properties are manifested through the reduction of significant inflammatory factors such as tumor necrosis factor-α, interleukin 1β and other related elements. Second, their antioxidant property is marked by an increase in the expression of superoxide dismuthase, glutathione peroxidase and other antioxidant enzymes. The third property is the antiapoptotic activity, characterized by decreased caspase-3 activity and lower expression of pro-apoptotic Bax in the striatum. Conclusion. Based on this comprehensive review, UDCA and TUDCA have the potential to be considered as a therapeutic agent in the management of the Parkinson's disease.

Keywords: Bile acids, pharmacology; Neurodegenerative diseases; Parkinson’s disease; Tauroursodeoxycholic acid; Ursodeoxycholic acid.