TY - JOUR
T1 - Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases
AU - Khalaf, Kareem
AU - Tornese, Paolo
AU - Cocco, Antoniangela
AU - Albanese, Alberto
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Amyotrophic lateral sclerosis
KW - Bile acids
KW - Disease-modifying
KW - Huntington’s disease
KW - Neurodegeneration
KW - Neuroprotection
KW - Parkinson’s disease
KW - Tauroursodeoxycholic acid
KW - Ursodeoxycholic acid
KW - Alzheimer’s disease
KW - Amyotrophic lateral sclerosis
KW - Bile acids
KW - Disease-modifying
KW - Huntington’s disease
KW - Neurodegeneration
KW - Neuroprotection
KW - Parkinson’s disease
KW - Tauroursodeoxycholic acid
KW - Ursodeoxycholic acid
UR - http://hdl.handle.net/10807/230319
U2 - 10.1186/s40035-022-00307-z
DO - 10.1186/s40035-022-00307-z
M3 - Article
SN - 2047-9158
VL - 11
SP - 33-1-33-17
JO - Translational Neurodegeneration
JF - Translational Neurodegeneration
ER -