An Update on Role of Bile Acids in Neurological Functions and Neurodegenerative Diseases: A Narrative Review

Abstract

Having previously reviewed the role of Bile Acids (BAs) in obesity, NAFLD/NASH/HCC and crosstalk of Gut Microbiome in numerous body disorders here we further attempted to assess part of BAs in normal brain physiology and in different Neurodegenerative Diseases (NDD). BAs constitute significant physiological molecules which apart from modulating nutrient absorption as well as metabolism in peripheral tissues influence neuromodulatory actions in the Central Nervous System (CNS). The formation of bile acids takes place basically from cholesterol in the liver by the canonical as well as alternate pathwaysor in the brain started by the neuron particular sterol Cholesterol-24 hydroxylase (CYP46A1) modulated pathway. Circulating BAs possess the capacity of crossing the Blood Brain Barrier (BBB) and thus gaining entry into the CNS via passive diffusion or through BAs transporters. Brain BAs act in the CNS via activation of membrane or nuclear receptors or influence the working of the neurotransmitter receptors. Indirect signal might be further given to the CNS through the Farsenoid X Receptor (FXR) based Fibroblast growth factor 15/19 (FGF15/19) pathway or the takeda G Protein Coupled (GPC) bile acid receptor 5 (TGR5) based Glucagon Like Peptide 1(GLP) pathway. In case of pathological situations, changes in BAs have been observed to probably aid in the pathogenesis of different neurological diseases. Of greater significance is the supplementationof hydrophilic amidated Ursodeoxycholic Acid (UDCA) or Tauroursodeoxycholic Acid (TUDCA) have been corroborated to illustrate therapeutic advantagesby hampering the neuroinflammatory reactions, apoptosis, Oxidative Stress (OS), Endoplasmic Reticulum (ER) stress, mitochondrial protection or work in the form of probable chaperone for correction of misfolding of proteins in the treatment of different neurological diseases. This yields opportunity of utilization of UDCA along with TUDCA in the treatment of different neurodegenerative diseases inclusive of Alzheimer’s disease; Parkinson’s disease, Huntingtons disease, Amyotrophic Lateral sclerosis, and prion disease.