Most
neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic
bile acids, particularly
tauroursodeoxycholic acid (
TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible
therapeutic use as disease-modifiers in
neurodegenerative diseases. Experimental evidence on the mechanisms underlying
TUDCA's neuroprotective action derives from animal models of
Alzheimer's disease,
Parkinson's disease, Huntington's diseases,
amyotrophic lateral sclerosis (ALS) and
cerebral ischemia. Preclinical studies indicate that
TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of
proteins. Furthermore, data from phase II clinical trials have shown
TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first
neurodegenerative disease being treated with hydrophilic
bile acids. While further clinical evidence is being accumulated for the other diseases,
TUDCA stands as a promising treatment for
neurodegenerative diseases.