[Retracted] A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction‐Related Diseases
Open accessAbstract
Bile acids are commonly known as one of the vital metabolites derived from cholesterol. The role of bile acids in glycolipid metabolism and their mechanisms in liver and cholestatic diseases have been well studied. In addition, bile acids also serve as ligands of signal molecules such as FXR, TGR5, and S1PR2 to regulate some physiological processes in vivo. Recent studies have found that bile acids signaling may also play a critical role in the central nervous system. Evidence showed that some bile acids have exhibited neuroprotective effects in experimental animal models and clinical trials of many cognitive dysfunction-related diseases. Besides, alterations in bile acid metabolisms well as the expression of different bile acid receptors have been discovered as possible biomarkers for prognosis tools in multiple cognitive dysfunction-related diseases. This review summarizes biosynthesis and regulation of bile acids, receptor classification and characteristics, receptor agonists and signaling transduction, and recent findings in cognitive dysfunction-related diseases.
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Altered bile acid profiles are observed in several neuropathologies associated with cognitive decline, such as Alzheimer's disease.
“Altered BA profiles have been observed in several neuropathologies associated with cognitive decline, such as Alzheimer’s disease (302, 324).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [324]
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Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.-U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., & Bäckhed, F. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.003 · Cited by 2,331 · cited 1× · see citing works
“The FXR affects primary BA synthesis by inhibiting the activity of CYP7A1 via inducing and binding to the fibroblast growth factor 15/19 (FGF 15/19) in ileum epithelial cells [27, 28].”
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069 · see citing works
Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Jia, W., Xie, G., & Jia, W. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.119 · Cited by 1,924 · cited 2× · see citing works
“a “messenger” in the “gut-brain” axis [10, 11].”
TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885 · see citing works
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865 · cited 1× · see citing works
“The FXR a ff ects primary BA synthesis by inhibiting the activity of CYP7A1 via inducing and binding to the fi broblast growth factor 15/19 (FGF 15/19) in ileum epithelial cells [27, 28].”
Bile acids: regulation of synthesis
Chiang, J. Y. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900010-jlr200 · Cited by 1,567 · see citing works
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513 · see citing works
Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
Biessels, G. J., & Despa, F. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0048-7 · Cited by 1,454 · cited 1× · see citing works
“According to the DCD development process or severity, it can be divided into asymptomatic preclinical MCI stage and dementia stage [133].”
Targeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422 · see citing works
Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
渡辺, 光., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21025 · Cited by 1,398 · cited 1× · see citing works
“There are two known pathways: the intestinal FXR/FGF19/ FGFR4 pathway [14] and the hepatic FXR/SHP pathway [45, 46].”
Identification of a nuclear receptor that is activated by farnesol metabolites
Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlmann, T., Noonan, D. J., Burka, L. T., McMorris, T., Lamph, W. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90530-8 · Cited by 1,210 · see citing works
Dietary lipids, gut microbiota and lipid metabolism
Schoeler, M., & Caesar, R. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09512-0 · Cited by 1,163 · cited 1× · see citing works
“a “messenger” in the “gut-brain” axis [10, 11].”
Consequences of bile salt biotransformations by intestinal bacteria
Ridlon, J. M., Harris, S. C., Bhowmik, S., Kang, D.-J., & Hylemon, P. B. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1127483 · Cited by 1,097 · see citing works
Huntington's disease: a clinical review
McColgan, P., & Tabrizi, S. J. (2017) · European Journal of Neurology · doi:10.1111/ene.13413 · Cited by 1,097 · cited 1× · see citing works
“It is caused by ampli fi ed mutations of CAG triplet repeats in exon 1 of the Huntingtin (HTT) gene and is associated with involuntary dance movements, mental and behavioral disorders, and impaired cognitive function [125].”
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.055 · Cited by 970 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · cited 1× · see citing works
“About 95% of BAs are actively ingested in the ileum through the apical sodium-dependent BA transporter (ASBT) at the tip of the brush edge of the small intestine and then enter the small intestinal epithelial cells [40, 41].”
Petersen, R. C. (2016) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000313 · Cited by 925 · see citing works
Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J., & Suchy, F. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011610200 · Cited by 804 · see citing works
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
Quigley, E. M. M. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0802-6 · Cited by 804 · cited 1× · see citing works
“The “ gut-brain axis ” has led researchers to recognize the profound impact of gut fl ora and its metabolites on the nervous system [83, 84].”
MahmoudianDehkordi, S., Arnold, M., Nho, K., Ahmad, S., Jia, W., Xie, G., Louie, G., Kueider‐Paisley, A., Moseley, M. A., Thompson, J. W., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.217 · Cited by 706 · see citing works
Roberts, M. S., Magnusson, B. M., Burczynski, F. J., & Weiß, M. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241100-00005 · Cited by 666 · cited 1× · see citing works
“Then, the BAs are reabsorbed by liver cells via Na+-dependent tauro-cholic cotransporting polypeptide (NTCP) and organic anion transporting polypeptides (OATPs) [42, 43].”
Alzheimer’s Disease: Past, Present, and Future
Bondi, M. W., Edmonds, E. C., & Salmon, D. P. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s135561771700100x · Cited by 649 · see citing works
Interaction of gut microbiota with bile acid metabolism and its influence on disease states
Staley, C. M., Weingarden, A. R., Khoruts, A., & Sadowsky, M. J. (2016) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-016-8006-6 · Cited by 582 · cited 1× · see citing works
“Another 5% of unabsorbed primary BAs in the intestinal tract are converted to secondary BAs by the gut microbiota through deconjugation, dehydroxyl dehydrogenation, and isomerization [25, 26].”
Metabolism of Cholesterol and Bile Acids by the Gut Microbiota
Gérard, P. (2013) · Pathogens · doi:10.3390/pathogens3010014 · Cited by 580 · see citing works
Ciaula, A. D., Garruti, G., Baccetto, R., Molina‐Molina, E., Bonfrate, L., Wang, D. Q. ‐., & Portincasa, P. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5493 · Cited by 573 · see citing works
Bile Acid Metabolism in Liver Pathobiology
Chiang, J. Y. L., & Ferrell, J. M. (2018) · Gene Expression · doi:10.3727/105221618x15156018385515 · Cited by 552 · see citing works
Song, Z., Cai, Y., Lao, X., Wang, X., Lin, X., Cui, Y., Kalavagunta, P. K., Liao, J., Jin, L., Shang, J., et al. (2019) · Microbiome · doi:10.1186/s40168-019-0628-3 · Cited by 505 · see citing works
Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease
Reddy, P. H., & Oliver, D. M. (2019) · Cells · doi:10.3390/cells8050488 · Cited by 496 · see citing works
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease
Kesika, P., Suganthy, N., Sivamaruthi, B. S., & Chaiyasut, C. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118627 · Cited by 479 · see citing works
Type 2 diabetes and cognitive dysfunction–towards effective management of both comorbidities
Srikanth, V., Sinclair, A. J., Hill-Briggs, F., Moran, C., & Biessels, G. J. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30118-2 · Cited by 465 · see citing works
Denson, L. A., Sturm, E., Echevarría, W., Zimmerman, T. L., Makishima, M., Mangelsdorf, D. J., & Karpen, S. J. (2001) · Gastroenterology · doi:10.1053/gast.2001.25503 · Cited by 460 · cited 1× · see citing works
“Moreover, FXR can inhibit BA liver reabsorption by downregulating the expression of liver reabsorption transporter NTCP via SHP dependent mechanism [60].”
Gao, B., Hagenbuch, B., Kullak-Ublick, G. A., Benke, D., Aguzzi, A., & Meier, P. J. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39041-x · Cited by 413 · see citing works
Bile acid transporters and regulatory nuclear receptors in the liver and beyond
Halilbasic, E., Claudel, T., & Trauner, M. A. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.08.002 · Cited by 397 · cited 1× · see citing works
“In addition, FXR also regulates BA transporters related to the enterohepatic circulation [59].”
The Role of the Gut Microbiota in Bile Acid Metabolism
Ramírez-Pérez, O., Cruz-Ramón, V., Chinchilla-López, P., & Méndez‐Sánchez, N. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5672 · Cited by 393 · see citing works
Role of cholesterol and sphingolipids in brain development and neurological diseases
Hussain, G., Wang, J., Rasul, A., Anwar, H., Imran, A., Qasim, M., Zafar, S., Kamran, S., Razzaq, A., Aziz, N., et al. (2019) · Lipids in Health and Disease · doi:10.1186/s12944-019-0965-z · Cited by 383 · see citing works
The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease
Hur, J.-Y., Frost, G. R., Wu, X., Crump, C., Pan, S. J., Wong, E., Barros, M., Li, T., Nie, P., Zhai, Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2681-2 · Cited by 382 · cited 1× · see citing works
“…studies, it is considered that the main pathogenesis of AD includes the degeneration of A β [90 – 92], hyperphosphorylation of Tau protein [93], the imbalance of choline [94], neuroin fl ammation [95, 96], abnormalities in neurotransmitters, and dysfunction of mitochondrial autophagy [97, 98].”
Self-citationTargeting the alternative bile acid synthetic pathway for metabolic diseases
Jia, W. P., Wei, M., Rajani, C., & Zheng, X. (2020) · Protein & Cell · doi:10.1007/s13238-020-00804-9 · Cited by 329 · see citing works
The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?
Megur, A., Baltriukienė, D., Bukelskienė, V., & Burokas, A. (2020) · Nutrients · doi:10.3390/nu13010037 · Cited by 323 · see citing works
The enterohepatic circulation of bile acids in mammals: form and functions
Alan, F. (2009) · Frontiers in bioscience · doi:10.2741/3399 · Cited by 321 · cited 1× · see citing works
“Then, the BAs are reabsorbed by liver cells via Na+-dependent taurocholic cotransporting polypeptide (NTCP) and organic anion transporting polypeptides (OATPs) [42, 43].”
Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes
Studer, E. J., Zhou, X., Zhao, R., Wang, Y., Takabe, K., Nagahashi, M., Pandak, W. M., Dent, P., Spiegel, S., Shi, R., et al. (2011) · Hepatology · doi:10.1002/hep.24681 · Cited by 319 · see citing works
Cognitive dysfunction in diabetes: how to implement emerging guidelines
Biessels, G. J., & Whitmer, R. A. (2019) · Diabetologia · doi:10.1007/s00125-019-04977-9 · Cited by 319 · cited 1× · see citing works
“[82, 130, 131].”
Keene, C. D., Rodrigues, C. M. P., Eich, T., Chhabra, M. S., Steer, C. J., & Low, W. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162362299 · Cited by 306 · see citing works
Plass, J. R. M., Mol, O., Heegsma, J., Geuken, M., Faber, K. N., Jansen, P. L. M., & Müller, M. M. (2002) · Hepatology · doi:10.1053/jhep.2002.31724 · Cited by 291 · see citing works
The G Protein-Coupled Bile Acid Receptor, TGR5, Stimulates Gallbladder Filling
Li, T., Holmstrom, S. R., Kır, S., Umetani, M., Schmidt, D. R., Kliewer, S. A., & Mangelsdorf, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0460 · Cited by 267 · see citing works
Quinn, M., McMillin, M., Galindo, C., Frampton, G., Pae, H. Y., & DeMorrow, S. (2014) · Digestive and Liver Disease · doi:10.1016/j.dld.2014.01.159 · Cited by 259 · cited 1× · see citing works
“Studies have found that some BAs may show increased BBB permeability both in vitro and in vivo through Rac1-dependent phosphorylation mechanisms of tight junction protein [117], which may be related to the activation of FXR and TGR5 [118 – 120].”
Animal models to study bile acid metabolism
Li, J., & Dawson, P. A. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.05.011 · Cited by 254 · cited 1× · see citing works
“For rodents like mice [23, 24], CDCA is converted to α -muricholic acid ( α -MCA) by the enzyme sterol-6b-hydroxylase (CYP2C70), and α -MCA can be epimerized (isomerized) to a 7 β -”
Tumminia, A., Vinciguerra, F., Parisi, M., & Frittitta, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113306 · Cited by 252 · see citing works
The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes
Alberto González-Regueiro, J., Moreno-Castañeda, L., Uribe, M., & Carlos Chávez-Tapia, N. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5494 · Cited by 247 · cited 1× · see citing works
“C C Changes in gut micro fl ora also alter the expression level of BSH, thus a ff ecting the composition of the host BA pool and BA signaling [10, 25] (more details are shown in Figure 1).”
Copple, B. L., & Li, T. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.12.007 · Cited by 235 · see citing works
FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity
Wang, X. X., Wang, D., Luo, Y., Myakala, K., Dobrinskikh, E., Rosenberg, A. Z., Levi, J., Kopp, J. B., Field, A. P., Hill, A., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017020222 · Cited by 226 · see citing works
12. Older Adults: Standards of Medical Care in Diabetes—2021
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc21-s012 · Cited by 225 · see citing works
Yanguas‐Casás, N., Barreda‐Manso, M. A., Nieto‐Sampedro, M., & Romero‐Ramírez, L. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25742 · Cited by 223 · see citing works
Cognitive dysfunction and migraine
Vurallı, D., Ayata, C., & Bolay, H. (2018) · The Journal of Headache and Pain · doi:10.1186/s10194-018-0933-4 · Cited by 222 · see citing works
Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease
Baloni, P., Funk, C. C., Yan, J., Yurkovich, J. T., Kueider-Paisley, A., Nho, K., Heinken, A., Jia, W., Mahmoudiandehkordi, S., Louie, G., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100138 · Cited by 211 · see citing works
Bile Acids and FXR: Novel Targets for Liver Diseases
Stofan, M., & Guo, G. L. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00544 · Cited by 202 · see citing works
Nunes, A. F., Amaral, J. D., Lo, A. C., Fonseca, M. B., Viana, R. J. S., Callaerts-Vegh, Z., D’Hooge, R., & Rodrigues, C. M. P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8256-y · Cited by 192 · see citing works
Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications
Hamed, S. A. (2017) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1293521 · Cited by 190 · see citing works
Vascular cognitive impairment and dementia
Gorelick, P. B., Counts, S., & Nyenhuis, D. L. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.015 · Cited by 187 · see citing works
Bile acid signaling in neurodegenerative and neurological disorders
Grant, S. M., & DeMorrow, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175982 · Cited by 185 · see citing works
Fabiani, E. D., Mitro, N., Anzulovich, A. C., Pinelli, A., Galli, G., & Crestani, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103270200 · Cited by 184 · cited 12× · see citing works
“In the liver and intestine, FXR acts as a BA sensor to negatively inhibit the expression of CYP7A1 and CYP8B1 through the FXR/FGF19/FGFR4 pathway [14] and the hepatic FXR/SHP pathway, respectively.”
InfluentialMicroglia activation in hepatic encephalopathy in rats and humans
Zemtsova, I. M., Görg, B., Keitel, V., Bidmon, H. J., Schrör, K., & Häussinger, D. (2011) · Hepatology · doi:10.1002/hep.24326 · Cited by 178 · cited 1× · see citing works
“Neuroin fl ammation is another important pathogenesis of HE, in which the activation of microglia acts as a key link [122] (more details are shown in Figure 3).”
Chemistry and Enterohepatic Circulation of Bile Acids† ‡ § ¶ # ‖ ** †† ‡‡ §§ ¶¶ ‖‖ ##
Hofmann, A. F. (1984) · Hepatology · doi:10.1002/hep.1840040803 · Cited by 175 · cited 1× · see citing works
“[44] (more details are shown in Figure 2).”
Heuman, D. M., Hylemon, P. B., & Vlahcevic, Z. R. (1989) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38276-6 · Cited by 163 · see citing works
Weiss, N., Hilaire, P. B. S., Colsch, B., Isnard, F., Attala, S., Schaefer, A., Amador, M. D. M., Rudler, M., Lamari, F., Sedel, F., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.07.046 · Cited by 158 · see citing works
Marksteiner, J., Blasko, I., Kemmler, G., Koal, T., & Humpel, C. (2017) · Metabolomics · doi:10.1007/s11306-017-1297-5 · Cited by 158 · see citing works
Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease
Pan, X., Elliott, C. T., McGuinness, B., Passmore, P., Kehoe, P. G., Hölscher, C., McClean, P. L., Graham, S. F., & Green, B. D. (2017) · Metabolites · doi:10.3390/metabo7020028 · Cited by 153 · see citing works
Defective Autophagy and Mitophagy in Aging and Alzheimer’s Disease
Tran, M. K., & Reddy, P. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.612757 · Cited by 152 · see citing works
Diversity of Bacteria Exhibiting Bile Acid-inducible 7α-dehydroxylation Genes in the Human Gut
Vital, M., Rud, T., Rath, S., Pieper, D. H., & Schlüter, D. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.07.012 · Cited by 149 · see citing works
Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism
Kwong, E. K., Li, Y., Hylemon, P. B., & Zhou, H. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2014.12.009 · Cited by 147 · see citing works
Bile Acid-Activated Receptors: A Review on FXR and Other Nuclear Receptors
Shin, D., & Wang, L. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_236 · Cited by 141 · cited 1× · see citing works
“There are mainly two kinds of BA – activated receptors [56, 57]: the nuclear receptors and the membrane receptors.”
Ridlon, J. M., Devendran, S., Alves, J. M. P., Doden, H. L., Wolf, P. G., Pereira, G. V., Ly, L. K., Volland, A., Takei, H., Nittono, H., et al. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1618173 · Cited by 137 · see citing works
Pandak, W. M., Ren, S., Marques, D., Hall, E., Redford, K. S., Mallonee, D. H., Bohdan, P. M., Heuman, D. M., Gil, G., & Hylemon, P. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205244200 · Cited by 135 · cited 1× · see citing works
“These metabolites are fi nally transported to the liver for the formation of CA and CDCA [20 – 22].”
Keene, C. D., Rodrigues, C. M. P., Eich, T., Linehan-Stieers, C., Abt, A., Kren, B. T., Steer, C. J., & Low, W. C. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7755 · Cited by 132 · see citing works
The Neuropsychology of Huntington's Disease
Snowden, J. S. (2017) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acx086 · Cited by 132 · cited 1× · see citing works
“However, unlike AD and other forms of dementia, patients may still retain some cognitive function in the middle and later stages of HD [126].”
TGR 5 signaling reduces neuroinflammation during hepatic encephalopathy
McMillin, M., Frampton, G. A., Tobin, R. P., Dusio, G. F., Smith, J., Shin, H. D., Newell‐Rogers, K., Grant, S. M., & DeMorrow, S. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13243 · Cited by 129 · see citing works
Cholesterol Biosynthesis and Uptake in Developing Neurons
Genaro-Mattos, T. C., Anderson, A., Allen, L. B., Korade, Z., & Mirnics, K. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00248 · Cited by 117 · see citing works
The Pharmacology of Bile Acids and Their Receptors
Fiorucci, S., & Distrutti, E. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_238 · Cited by 117 · see citing works
Huang, F., Pariante, C. M., & Borsini, A. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.09.021 · Cited by 117 · see citing works
Bile acid metabolism and circadian rhythms
Yang, Y., & Zhang, J. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00152.2020 · Cited by 114 · cited 1× · see citing works
“About 95% of BAs are actively ingested in the ileum through the apical sodium-dependent BA transporter (ASBT) at the tip of the brush edge of the small intestine and then enter the small intestinal epithelial cells [40, 41].”
McMillin, M., Frampton, G. A., Grant, S. M., Khan, S. H., Diocares, J., Petrescu, A. D., Wyatt, A., Kain, J., Jefferson, B., & DeMorrow, S. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00191 · Cited by 111 · see citing works
Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice
Kim, K. H., Choi, S., Zhou, Y., Kim, E. Y., Lee, J. M., Saha, P. K., Anakk, S., & Moore, D. D. (2017) · Hepatology · doi:10.1002/hep.29199 · Cited by 107 · cited 1× · see citing works
“There are two known pathways: the intestinal FXR/FGF19/ FGFR4 pathway [14] and the hepatic FXR/SHP pathway [45, 46].”
Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure
McMillin, M., Frampton, G. A., Quinn, M. A., Ashfaq, S., Santos, M. D. L., Grant, S. M., & DeMorrow, S. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.10.005 · Cited by 106 · cited 2× · see citing works
“Similarly, increased total BA content in brain tissue has been detected in a rodent model of HE [114, 115].”
MAFG Is a Transcriptional Repressor of Bile Acid Synthesis and Metabolism
Vallim, T. Q. D. A., Tarling, E. J., Ahn, H., Hagey, L. R., Romanoski, C. E., Lee, R. G., Graham, M. J., Motohashi, H., Yamamoto, M. P., & Edwards, P. A. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.01.007 · Cited by 104 · cited 1× · see citing works
“In addition, a recent study showed that the FXRmediated transcriptional repressor, V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), can directly inhibit BA synthesis-related genes such as CYP8B1 and regulate BA composition, which may have a significant impact on liver metabolism and related disea…”
Hou, L., Yang, L., Chang, N., Zhao, X., Zhou, X., Dong, C., Liu, F., Yang, L., & Li, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01149 · Cited by 102 · see citing works
Wu, X. G., Lv, Y., Du, Y., Chen, F., Reed, M. N., Hu, M. Y., Suppiramaniam, V. D., Tang, S., & Hong, H. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.018 · Cited by 100 · see citing works
Bazzari, F. H., Abdallah, D. M., & El-Abhar, H. S. (2019) · Molecules · doi:10.3390/molecules24101992 · Cited by 98 · see citing works
Bile Acid-Activated Receptors: GPBAR1 (TGR5) and Other G Protein-Coupled Receptors
Keitel, V., Stindt, J., & Häussinger, D. (2019) · Handbook of Experimental Pharmacology · doi:10.1007/164_2019_230 · Cited by 98 · cited 2× · see citing works
“TGR5 is a trans-membrane G-protein-coupled receptor (GPCR) for BAs that is widely expressed in the epithelial cells of multiple tissues, including in the intestine, spleen, cholangiocytes, gallbladder, hepatic sinusoidal endothelial cells, and hepatic macrophages [56].”
Bell, S., Barnes, K., Clemmens, H., Alrafiah, A., Al-ofi, E. A., Leech, V., Bandmann, O., Shaw, P. J., Blackburn, D. J., Ferraiuolo, L., et al. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.08.019 · Cited by 97 · see citing works
Varma, V. R., Wang, Y., An, Y., Varma, S., Bilgel, M., Doshi, J., Legido-Quigley, C., Delgado, J. C., Oommen, A. M., Roberts, J. A., et al. (2021) · PLOS Medicine · doi:10.1371/journal.pmed.1003615 · Cited by 97 · cited 1× · see citing works
“In the latest large-scale clinical study [103], researchers conducted three experiments to investigate whether abnormal cholesterol catabolism, through its conversion into BAs, is associated with the progression of AD and VD.”
Axelson, M., Ellis, E. C. S., Mörk, B., Garmark, K., Abrahamsson, A., Björkhem, I., Ericzon, B., & Einarsson, C. (2000) · Hepatology · doi:10.1053/jhep.2000.7877 · Cited by 94 · see citing works
Bello‐Chavolla, O. Y., Antonio‐Villa, N. E., Vargas‐Vázquez, A., Ávila‐Funes, J. A., & Aguilar-Salinas, C. A. (2019) · Current Diabetes Reviews · doi:10.2174/1573399815666190129155654 · Cited by 93 · see citing works
Whole body cholesterol metabolism is impaired in Huntington's disease
Leoni, V., Mariotti, C., Nanetti, L., Salvatore, E., Squitieri, F., Bentivoglio, A. R., del Poggio, M. B., Piacentini, S., Monza, D., Valenza, M., et al. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.03.025 · Cited by 90 · see citing works
Jia, W., Rajani, C., Kaddurah‐Daouk, R., & Li, H. (2020) · Medicinal Research Reviews · doi:10.1002/med.21653 · Cited by 88 · see citing works
Chen, W., & Chiang, J. Y. L. (2003) · Gene · doi:10.1016/s0378-1119(03)00631-0 · Cited by 86 · cited 1× · see citing works
“It is initiated by mitochondrial sterol 27-hydroxylase (CYP27A1) which is distributed in multiple tissues and macrophages [17, 18].”
Xie, G., Wang, X., Jiang, R., Zhao, A., Yan, J., Zheng, X., Huang, F., Liu, X., Panee, J., Rajani, C., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.030 · Cited by 84 · cited 1× · see citing works
“Moreover, BAs can also enter the brain by active transport via apical sodium-dependent BA transporters (ASBT) [121].”
McMillin, M., Frampton, G. A., Thompson, M., Galindo, C., Standeford, H. A., Whittington, E., Alpini, G. D., & DeMorrow, S. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-121 · Cited by 82 · cited 1× · see citing works
“…chemokine ligand 2 (CCL2) in neurons was increased accompanied by a decrease in the anti-in fl ammatory chemokine fractalkine in a HE mouse model, resulting in a disruption of the balance between pro-and anti-in fl ammatory signals acting on microglia, leading to the microglia activation [123, 124].”
Suppression of the HPA axis during cholestasis can be attributed to hypothalamic bile acid signaling
McMillin, M., Frampton, G., Quinn, M., Divan, A., Grant, S., Patel, N., Newell-Rogers, K., & DeMorrow, S. (2015) · Molecular Endocrinology · doi:10.1210/me.2015-1087 · Cited by 82 · see citing works
Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer’s Disease
Shao, Y., Ouyang, Y., Li, T., Liu, X., Xu, X., Li, S., Xu, G., & Le, W. (2020) · Aging and Disease · doi:10.14336/ad.2020.0217 · Cited by 79 · cited 1× · see citing works
“Alteration in BA metabolism and its associated receptors have also been found in the patients or animal models of cognitive dysfunction-associated diseases in the latest research [12, 13].”
Björkhem, I., Araya, Z., Rudling, M., Angelin, B., Einarsson, C., & Wikvall, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202343200 · Cited by 76 · cited 1× · see citing works
“It is initiated by mitochondrial sterol 27-hydroxylase (CYP27A1) which is distributed in multiple tissues and macrophages [17, 18].”
Stravitz, R. T., Vlahcevic, Z. R., Russell, T. L., Heizer, M. L., Avadhani, N. G., & Hylemon, P. B. (1996) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00282-0 · Cited by 75 · see citing works
Khan, A. A., Chow, E. C. Y., van Loenen-Weemaes, A. M., Porte, R. J., Pang, K. S., & Groothuis, G. M. M. (2009) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2009.01.006 · Cited by 75 · see citing works
Role of vitamin D receptor in the regulation of CYP3A gene expression
Qin, X., & Wang, X. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.03.005 · Cited by 74 · see citing works
Wu, X. G., Lv, Y., Du, Y., Hu, M. Y., Reed, M. N., Long, Y., Suppiramaniam, V. D., Hong, H., & Tang, S. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.08.016 · Cited by 73 · see citing works
Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease
McDaid, J., Mustaly-Kalimi, S., & Stutzmann, G. E. (2020) · Cells · doi:10.3390/cells9122655 · Cited by 73 · cited 1× · see citing works
“In addition, recent studies have revealed that gut microbiota dysregulation [99, 100] and Ca2+ in fl ux [101, 102] are also closely associated with AD.”
Cholesterol 24-hydroxylase: Brain cholesterol metabolism and beyond
Moutinho, M., Nunes, M. J., & Rodrigues, E. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.09.011 · Cited by 72 · cited 1× · see citing works
“The BA synthesis pathway in the brain is catalyzed by neuron-speci fi c sterol 24-hydroxylase (CYP46A1) to convert cholesterol into 24( S )-hydroxycholesterol [51] (shown in Figure 3).”
Cheng, J., Fang, Z., Kim, J. H., Krausz, K. W., Tanaka, N., Chiang, J. Y. L., & Gonzalez, F. J. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m044420 · Cited by 71 · see citing works
Gut Microbiota‐Bile Acid Crosstalk in Diarrhea‐Irritable Bowel Syndrome
Zhan, K., Zheng, H., Jian-qing, L., Wu, H., Qin, S., Luo, L., & Huang, S. (2020) · BioMed Research International · doi:10.1155/2020/3828249 · Cited by 70 · see citing works
Diabetes-Related Neurological Implications and Pharmacogenomics
Rojas-Carranza, C. A., Bustos, R., Pinzón, C. J. P., Márquez, Y. V. A., Gomez-Bello, R. M., & Cañadas‐Garre, M. (2018) · Current Pharmaceutical Design · doi:10.2174/1381612823666170317165350 · Cited by 67 · see citing works
Zangerolamo, L., Vettorazzi, J. F., Solon, C., Bronczek, G. A., Engel, D. F., Kurauti, M. A., Soares, G. M., Rodrigues, K. S., Velloso, L. A., Boschero, A. C., et al. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111116 · Cited by 66 · see citing works
Chand, D., Panigrahi, P., Varshney, N. K., Ramasamy, S., & Suresh, C. G. (2018) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2018.01.003 · Cited by 64 · see citing works
Can We Treat Neuroinflammation in Alzheimer’s Disease?
Sánchez‐Sarasúa, S., Fernández-Pérez, I., Espinosa‐Fernández, V., Sánchez‐Pérez, A. M., & Ledesma, J. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228751 · Cited by 62 · see citing works
Ramalho, R. M., Nunes, A. F., Dias, R. B., Amaral, J. D., Lo, A. C., D’Hooge, R., Sebastião, A. M., & Rodrigues, C. M. P. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.04.018 · Cited by 60 · see citing works
Wu, X., Liu, C., Chen, L., Du, Y.-F., Hu, M., Reed, M. N., Long, Y., Suppiramaniam, V., Hong, H., & Tang, S.-S. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.065 · Cited by 56 · see citing works
Greotti, E., Capitanio, P., Wong, A., Pozzan, T., Pizzo, P., & Pendin, D. (2019) · Cell Calcium · doi:10.1016/j.ceca.2019.02.005 · Cited by 55 · see citing works
Cao, C., Dai, L., Mu, J., Wang, X., Hong, Y., Zhu, C., Jin, L., & Li, S. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.09.019 · Cited by 47 · see citing works
Seyedsadr, M., Weinmann, O., Amorim, A., Ineichen, B., Egger, M., Mirnajafi-zadeh, J., Becher, B., Javan, M., & Schwab, M. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.11.018 · Cited by 47 · see citing works
Sun, C., Gao, M., Wang, F., Yun, Y., Sun, Q., Guo, R., Yan, C., Sun, X., & Li, Y. (2020) · Biomedical Chromatography · doi:10.1002/bmc.4875 · Cited by 43 · cited 1× · see citing works
“Alteration in BA metabolism and its associated receptors have also been found in the patients or animal models of cognitive dysfunction-associated diseases in the latest research [12, 13].”
McMillin, M., Grant, S. M., Frampton, G. A., Petrescu, A. D., Kain, J., Williams, E., Haines, R., Canady, L., & DeMorrow, S. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.02.008 · Cited by 38 · see citing works
Eyssen, H., Eldere, J. V., Parmentier, G. G., Huijghebaert, S., & Mertens, J. (1985) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(85)90176-1 · Cited by 36 · see citing works
Waking action of ursodeoxycholic acid (UDCA) involves histamine and GABAA receptor block
Yanovsky, Y., Schubring, S. R., Yao, Q., Zhao, Y., Li, S., May, A., Haas, H. L., Lin, J.-S., & Sergeeva, O. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042512 · Cited by 34 · see citing works
Plasma Metabolomic Profiling of Patients with Diabetes-Associated Cognitive Decline
Zhang, L., Li, M., Zhan, L., Lu, X., Liang, L., Su, B., Sui, H. X., Gao, Z., Li, Y., Liu, Y., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126952 · Cited by 29 · see citing works
Early Mitochondrial Fragmentation and Dysfunction in a Drosophila Model for Alzheimer’s Disease
Wang, X., & Davis, R. L. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02107-w · Cited by 26 · cited 1× · see citing works
“…studies, it is considered that the main pathogenesis of AD includes the degeneration of A β [90 – 92], hyperphosphorylation of Tau protein [93], the imbalance of choline [94], neuroin fl ammation [95, 96], abnormalities in neurotransmitters, and dysfunction of mitochondrial autophagy [97, 98].”
Sun, X., Han, R., Cheng, T., Zheng, Y., Xiao, J., So, K., & Zhang, L. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.184 · Cited by 24 · see citing works
Yahiro, K., Setoguchi, T., & Katsuki, T. (1980) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39827-8 · Cited by 23 · see citing works
Diabetic Cognitive Dysfunction: From Bench to Clinic
Zhou, J., Zhang, Z., Zhou, H., & Qian, G. (2020) · Current Medicinal Chemistry · doi:10.2174/1871530319666190206225635 · Cited by 22 · cited 1× · see citing works
“[82, 130, 131].”
Wang, X., Wang, F., Zhang, Y., Xiong, H., Zhang, Y., Zhuang, P., & Zhang, Y. (2018) · Toxicology Letters · doi:10.1016/j.toxlet.2018.01.006 · Cited by 20 · see citing works
Norlin, M. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30114-0 · Cited by 19 · cited 4× · see citing works
“3 β -Hydroxy-5-cholinic acid is catalyzed by a nonspeci fi c oxysterol 7 α -hydroxylase (CYP7B1) [19] for the formation of 3 β , 7 α -dihydroxy-5-cholinergic acid, followed by HSD3B1/3B2 to synthesize 7a-hydroxy-3-oxo-4-cholesterol acid.”
InfluentialBignante, E. A., Ponce, N. E., Heredia, F., Musso, J., Krawczyk, M. C., Millan, J., Pigino, G. F., Inestrosa, N. C., Boccia, M. M., & Lorenzo, A. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.12.013 · Cited by 18 · see citing works
Targeting Xenobiotic Nuclear Receptors PXR and CAR to Prevent Cobicistat Hepatotoxicity
Shehu, A. I., Zhu, J., Li, J., Lu, J. L., McMahon, D., Xie, W., Gonzalez, F. J., & Ma, X. (2021) · Toxicological Sciences · doi:10.1093/toxsci/kfab023 · Cited by 18 · see citing works
Setoguchi, T., Higashi, S., Tateno, S., Yahiro, K., & Katsuki, T. (1984) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34468-0 · Cited by 17 · see citing works
S1PR2 Knockdown Promotes Migration and Invasion in Multiple Myeloma Cells via NF-κB Activation
Pang, M., Li, C., Zheng, D., Wang, Y., Wang, J., Zhang, W., Li, F., & Jing, H. (2020) · Cancer Management and Research · doi:10.2147/cmar.s237330 · Cited by 17 · see citing works
Czarnecka, A. M., Milewski, K., Albrecht, J., & Zielińska, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207750 · Cited by 16 · cited 1× · see citing works
“Studies have found that some BAs may show increased BBB permeability both in vitro and in vivo through Rac1-dependent phosphorylation mechanisms of tight junction protein [117], which may be related to the activation of FXR and TGR5 [118 – 120].”
Choline as a prevention for Alzheimer’s disease
Velázquez, R., Winslow, W., & Mifflin, M. A. (2020) · Aging · doi:10.18632/aging.102849 · Cited by 13 · see citing works
Koike, S., Miyaji, Y., Sano, H., Aikawa, N., Kai, M., Kasahara, S., Suzuki, T., Nishimoto‐Kusunose, S., & Ogasawara, Y. (2021) · Analytical Sciences · doi:10.2116/analsci.20p429 · Cited by 13 · see citing works
Zou, Y., Fan, F., Fang, Y., Li, P., Xia, J., Shen, X., Liu, Q., & Hu, Q. (2021) · eFood · doi:10.2991/efood.k.210125.001 · Cited by 12 · see citing works
Bile acid structure and intestinal absorption in the animal model.
Aldini, R., Roda, A., Montagnani, M., & Roda, E. (1995) · PubMed · Cited by 7 · see citing works
Ren, J. (2021) · Food Frontiers · doi:10.1002/fft2.62 · Cited by 7 · see citing works
MafG, A Novel Target of FXR that Regulates Bile Acid Homeostasis
Yang, Y. M., Roh, Y. S., & Seki, E. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.10.014 · Cited by 6 · cited 1× · see citing works
“…that the FXR-mediated transcriptional repressor, V-maf avian musculo-aponeurotic fi brosarcoma oncogene homolog G (MAFG), can directly inhibit BA synthesis-related genes such as CYP8B1 and regulate BA composition, which may have a signi fi cant impact on liver metabolism and related disease [47, 48].”
Delgadillo, A. T., Padilla, F. J. B., Hernandez, C., Ramos, J., & Esquivel, M. U. (2009) · PubMed · Cited by 3 · see citing works
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Bays, H. E., Kirkpatrick, C. F., Maki, K. C., Toth, P. P., Morgan, R. T., Tondt, J., Christensen, S. M., Dixon, D. L., & Jacobson, T. A. (2024) · Journal of clinical lipidology · doi:10.1016/j.jacl.2024.04.001 · Cited by 190 · see citing works
Bays, H. E., Kirkpatrick, C. F., Maki, K. C., Toth, P. P., Morgan, R. T., Tondt, J., Christensen, S. M., Dixon, D. L., & Jacobson, T. A. (2024) · Obesity Pillars · doi:10.1016/j.obpill.2024.100108 · Cited by 101 · see citing works
“That said, cholesterol can be broken down into bile acids for excretion, mostly in the liver [116] (although some cholesterol breakdown into bile acids can occur in other tissues such as brain [117]).”
BackgroundConnecting the Gut Microbiota and Neurodegenerative Diseases: the Role of Bile Acids
Wang, S., Xu, C., Liu, H., Wei, W., Zhou, X., Qian, H., Zhou, L., Zhang, H., Wu, L. M., Chen, Z., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03340-9 · Cited by 50 · see citing works
“This is the enterohepatic circulation of BAs [16] (Fig.”
BackgroundInfluentialMicroglia and gut microbiota: A double-edged sword in Alzheimer's disease
Bano, N., Khan, S., Ahamad, S., Kanshana, J. S., Dar, N. J., Khan, S. J., Nazir, A., & Bhat, S. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102515 · Cited by 49 · see citing works
The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke
Wu, L., Zhao, M., Li, M., Guo, Q., Zhenxing, R., Xiaojiao, Z., & Chen, T. (2022) · PROTEOMICS · doi:10.1002/pmic.202100324 · Cited by 47 · see citing works
“Recent studies suggest that BAs may play both positive and negative roles in the central nervous system, and can involve in the physiology and pathophysiology of the brain [6, 16].”
BackgroundBile acid profile associated with CSF and PET biomarkers in Alzheimer’s disease
Nabizadeh, F., Valizadeh, P., Fallahi, M. S., & Initiative, A. D. N. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-024-02729-3 · Cited by 37 · see citing works
“Several metabolomics investigations conducted on individuals with AD or animal models have revealed substantial disparities in the composition and levels of BAs present in AD patients’ serum and brain tissue compared to healthy individuals [17–23].”
BackgroundCai, D., Zhao, Z., Zhao, L., Dong, Y., Wang, L., Zhao, S., & Li, Q. (2022) · Nutrients · doi:10.3390/nu14204420 · Cited by 25 · see citing works
“Studies have demonstrated that bile acids act as metabolic regulators and nutrient sensors to regulate glucose and lipid metabolism, and immune response [20].”
BackgroundThe role of the gut microbiome and its metabolites in cerebrovascular diseases
Xu, H., Xu, Z., Long, S., Li, Z., Jiang, J., Zhou, Q., Huang, X., Wu, X., Wei, W., & Li, X. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1097148 · Cited by 26 · see citing works
“Recent studies have implicated BA in cerebrovascular disease in both positive and negative functions and are directly involved in the physiological activities and pathological processes of the brain (Weng et al., 2022).”
BackgroundThe FXR mediated anti-depression effect of CDCA underpinned its therapeutic potentiation for MDD
Li, H., Zhu, X., Xu, J., Li, L., Kan, W., Bao, H., Xu, J., Wang, W., Yang, Y., Chen, P., et al. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109626 · Cited by 22 · see citing works
Neuroactive metabolites and bile acids are altered in extremely premature infants with brain injury
Pristner, M., Wasinger, D., Seki, D., Klebermaß-Schrehof, K., Berger, A., Berry, D., Wisgrill, L., & Warth, B. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101480 · Cited by 22 · see citing works
Bile acid modulation by gut microbiota: a bridge to understanding cognitive health
Sabahat, S. E., Saqib, M., Talib, M., Shaikh, T. G., Khan, T., & Kailash, S. J. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000002433 · Cited by 18 · see citing works
“…with some bile acids, such as ursodeoxycholic acid (UDCA) and taur-oursodeoxycholic acid (TUDCA), has been shown to decrease neuroin fl ammation, increase mitochondrial function, and prevent A β -induced synaptic toxicity and amyloid precursor protein processing in APP/PS1 mice or neurons [25] .”
BackgroundInfluentialExploring the Intricate Nexus of Sarcopenia and Cognitive Impairment
Xing, Y., Li, X., & Ma, L. (2023) · Aging and Disease · doi:10.14336/ad.2023.1013 · Cited by 16 · see citing works
Hepatic interoception in health and disease
Berthoud, H., Münzberg, H., Morrison, C. D., & Neuhuber, W. (2024) · Autonomic Neuroscience · doi:10.1016/j.autneu.2024.103174 · Cited by 17 · see citing works
Samartsev, V. N., Khoroshavina, E. I., Pavlova, E. K., Dubinin, M. V., & Semenova, A. A. (2023) · Membranes · doi:10.3390/membranes13050472 · Cited by 11 · see citing works
Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial
Harnisch, L.-O., Neugebauer, S., Mihaylov, D., Eidizadeh, A., Zechmeister, B., Maier, I., & Moerer, O. (2023) · Biomedicines · doi:10.3390/biomedicines11112947 · Cited by 10 · see citing works
“In many, mainly chronic, neurologic disorders, bile acid metabolism has been found to be altered, and bile acids can be detected in quantifiable and even rather high concentrations in cerebrospinal fluid and/or brain parenchyma [13–17].”
BackgroundPinheiro, F. I., Araújo-Filho, I., Rêgo, A. C. M., de Azevedo, E. P., Cobucci, R. N., & Gúzen, F. P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102250 · Cited by 10 · see citing works
Decoding TGR5: A comprehensive review of its impact on cerebral diseases
Zhang, Z., Zhang, Y., Peng, H., Yu, Q., Kang, X., Liu, Y., Zheng, Y., Cheng, F., Wang, X., & Li, F. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107671 · Cited by 10 · see citing works
Plasma unconjugated bile acids as novel biomarker for schizophrenia
Koike, S., Miyaji, Y., Suzuki, K., Miyashita, M., Itokawa, M., Arai, M., & Ogasawara, Y. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.09.110 · Cited by 7 · see citing works
Tzeng, I., & Hsieh, T.-H. J. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2178417 · Cited by 7 · see citing works
“The conclusion made by a review article that elucidated the effect of anti-diabetic medications, which could be used as interventions for the prevention of dementia, is still disputable [24].”
BackgroundCore biomarkers analysis benefit for diagnosis on human intrahepatic cholestasis of pregnancy
Fang, Y., Kang, Z., Zhang, W., Xiang, Y., Cheng, X., Gui, M., & Fang, D. (2024) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-024-06730-6 · Cited by 5 · see citing works
“…glycocholic acid (GCA), taurolithocholic acid (TLCA), glycholitho-cholic acid (GLCA), glychodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), glycochenodeoxycholic acid (GCDCA), tauroursodeoxycholic acid (TUDCA), glycoursodeoxy-cholic acid (GUDCA) [3, 4].”
BackgroundChong, J., Zhou, Y., Li, Z., Li, X., Zhang, J., Cao, H., Ma, J., Ge, L., Zhong, H., & Sun, J. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1610956 · Cited by 3 · see citing works
Mireault, M., Rose, C. F., Karvellas, C. J., & Sleno, L. (2024) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.9731 · Cited by 2 · see citing works
Zahiri, J., Mirzaie, M., Duan, K., Xiao, Y., Aamodt, C., Yang, X., Nazari, S., Andreason, C., Lopez, L., Barnes, C. C., et al. (2024) · medRxiv · doi:10.1101/2024.09.17.24313857 · Cited by 2 · see citing works
Xiong, Y., Xiong, Y., Yang, H., Guo, F., Yin, J., Liao, S., Chen, Z., Zhang, W., Zhou, H.-H., Weng, C., et al. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100116 · Cited by 1 · see citing works
Retracted: A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction-Related Diseases
Longevity, O. M. A. C. (2024) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2024/9764647
RetractedZhang, G. (2025) · Environmental Disease · doi:10.4103/ed.ed_5_25
Ma, L., Blair, R. V., Liu, Y.-Z., Wang, X., Vincent, E., Yu, C. K., Doyle‐Meyers, L. A., Zhang, C., Saied, A. A., Le, A., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7802364/v1
THE ROLE OF LIPIDS AND LIPOPROTEINS IN THE PATHOGENESIS OF ATHEROSCLEROSIS
Tahir, I. M. (2025) · Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії · doi:10.31718/2077-1096.25.3.274
Ariaei, A., Zamiri, R., Ghasemi, A., Rezayani, B., Rezayani, S., Ezatpour, A., Farshidi, N., Sheikhi, E. A., & Roghanian, A. (2026) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2026.06.003
“Deoxycholic acid (DCA) is a secondary bile acid that facilitates the absorption of fats in the intestine (Weng et al., 2022).”
Rui, L. I., Li-Yun, S. H. A., You-Guan, H. E. N. G., & Shen, W.-Q. (2026) · Shengming kexue · doi:10.3724/cbls.2026077
Pavlova, S. I., Samartsev, V. N., Kuzmina, E. I., Zainutdinova, G. I., & Dubinin, M. V. (2026) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-026-10129-7
“The primary bile acids, cholic acid and chenodeoxycholic acid (CDCA), are synthesized in liver cells and, during cholestasis caused by impaired bile flow, can accumulate in cells of this organ (Schulz et al., 2013; Shulpekova et al., 2022; Weng et al., 2022).”
- Authors
- Weng, Z.-B., Chen, Y.-R., Lv, J.-T., Wang, M.-X., Chen, Z.-Y., Zhou, W., Shen, X.-C., Zhan, L.-B., & Wang, F.
- Affiliations
- Nanjing University of Finance and Economics (CN)
- Nanjing University of Chinese Medicine (CN)
- Corresponding author
- Wang, Fang
- ORCID
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2022-01
- Volume
- 2022
- Issue
- 1
- Pages
- 4289383-4289383
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC8933076
- OpenAlex
- W4220908394
- Cited by
- 32
- References
- 140
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 7 · 2022: 4
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Nanjing University of Chinese Medicine (NZY81903940)
- Natural Science Foundation of Jiangsu Province (BK20180817, BK20181415, BK20190804)
- National Natural Science Foundation of China (81730111, 32172139, 81903940)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- bile acids, bile acid metabolism, bile acid signaling, cognitive impairment, neuroprotection, farnesoid X receptor, TGR5, S1PR2, bile acid receptors, cholesterol metabolism, biomarkers, signal transduction
- MeSH terms
- Animals, Bile Acids and Salts, Liver, Signal Transduction, Lipid Metabolism, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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