Bile Acid Signaling in Neurodegenerative and Neurological Disorders

Abstract

Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase and ethanolamides metabolism with Alzheimer’s disease

“…Interestingly, several bile acid and steroid differences in AD were gender specific. Few studies reports gender specific action of TUDCA and UDCA on ER stress markers in rodent model for the prion disease [29]. These findings further support the importance of gender focused approaches when investigating cholesterol-derived metabolism in the context of AD, as established with regards to the links between ApoE4 and AD risk in post-menopausal women [30].…”

Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase and ethanolamides metabolism with Alzheimer’s disease

“…Considering that the current manuscript focuses on AD related differences in the fasting state, further studies probing postprandial bile acid metabolism and AD are suggested. Interestingly, several bile acid and steroid differences in AD were gender speci c. Few studies reports gender speci c action of TUDCA and UDCA on ER stress markers in rodent model for the prion disease (30). These ndings further support the importance of gender focused approaches when investigating cholesterol-derived metabolism in the context of AD, as established with regards to the links between ApoE4 and AD risk in post-menopausal women (31).…”

Physiology and Physical Chemistry of Bile Acids

“…Furthermore, BAs work in the body as hormones, being signaling molecules for the expression of genes and regulators of different metabolic paths. The physiological roles of BAs briefly summarized here and comprehensively overviewed by other specialist reports [210][211][212][213][214], opened the field for an extensive investigation of BAs and BADs use in biomedical applications including antimicrobics, anti-cholesterol drugs, regulator of dietary lipid uptake and drug carriers in co-formulations with other molecules (e.g., lipids and polymers). The application possibilities broaden even more when adopting BADs.…”