Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain DOI Creative Commons

Yuning Wu,

Yuxin Qiu,

Minzhi Su

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(7), С. 1981 - 1998

Опубликована: Март 7, 2023

Abstract Aims Beyond digestion, bile acids have been recognized as signaling molecules with broad paracrine and endocrine functions by activating plasma membrane receptor (Takeda G protein‐coupled 5, TGR5) the nuclear farnesoid X (FXR). The present study investigated role of in alleviating neuropathic pain TGR5 FXR. Method Neuropathic was induced spared nerve injury (SNI) sciatic nerve. or FXR agonist injected intrathecally. Pain hypersensitivity measured Von Frey test. amount detected using a acid assay kit. Western blotting immunohistochemistry were used to assess molecular changes. Results We found that downregulated, whereas expression cytochrome P450 cholesterol 7ahydroxylase (CYP7A1), rate‐limiting enzyme for synthesis, upregulated exclusively microglia spinal dorsal horn after SNI. Furthermore, receptors increased glial cells GABAergic neurons on day 7 Intrathecal injection either SNI alleviated established mechanical allodynia mice, effects blocked antagonist. Bile agonists inhibited activation ERK pathway horn. All above allodynia, cells, abolished intrathecal GABA A antagonist bicuculline. Conclusion These results suggest counteracts allodynia. effect mediated potentiating function receptors, which then neuronal sensitization

Язык: Английский

Stimulating VAPB-PTPIP51 ER-mitochondria tethering corrects FTD/ALS mutant TDP43 linked Ca2+ and synaptic defects DOI Creative Commons
Andrea Markovinović, Sandra M. Martín‐Guerrero, Gábor M. Mórotz

и другие.

Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 23, 2024

Abstract Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are clinically linked major neurodegenerative diseases. Notably, TAR DNA-binding protein-43 (TDP43) accumulations hallmark pathologies of FTD/ALS mutations in the gene encoding TDP43 cause familial FTD/ALS. There no cures for display damage to a broad range physiological functions, many which regulated by signaling between endoplasmic reticulum (ER) mitochondria. This is mediated VAPB-PTPIP51 tethering proteins that serve recruit regions ER mitochondrial surface so as facilitate inter-organelle communications. Several studies have now shown disrupted ER-mitochondria including breaking tethers features other genetic insults, this involves activation glycogen kinase-3β (GSK3β). Such findings prompted suggestions correcting interaction may be broadly therapeutic. Here we provide evidence support notion. We show overexpression VAPB or PTPIP51 enhance corrects mutant induced inositol 1,4,5-trisphosphate (IP3) receptor delivery Ca 2+ mitochondria primary function tethers, synaptic function. Moreover, ursodeoxycholic acid (UDCA), an FDA approved drug diseases therapy whose precise therapeutic target unclear, interaction. also effect inhibition GSK3β. Thus, value age-related

Язык: Английский

Процитировано

11
Physiological Role of Bile Acids Modified by the Gut Microbiome DOI Creative Commons
Yoshimitsu Kiriyama, Hiromi Nochi

Microorganisms, Год журнала: 2021, Номер 10(1), С. 68 - 68

Опубликована: Дек. 30, 2021

Bile acids (BAs) are produced from cholesterol in the liver and termed primary BAs. Primary BAs conjugated with glycine taurine then released into intestine via gallbladder. After deconjugation of or by gut microbiome, converted secondary microbiome through modifications such as dehydroxylation, oxidation, epimerization. Most reabsorbed transported to liver, where both rereleased intestine. Thus, unconjugated Bas, well BAs, have been modified microbiome. Some spill systemic circulation, they bind a variety nuclear cell-surface receptors tissues, whereas some not terminal ileum. play crucial roles physiological regulation various tissues. Furthermore, factors, diet, age, antibiotics influence BA composition. Here, we review recent findings regarding metabolic, immune, nervous systems.

Язык: Английский

Процитировано

53
The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke DOI

Lirong Wu,

Mingliang Zhao,

Mengci Li

и другие.

PROTEOMICS, Год журнала: 2022, Номер 22(15-16)

Опубликована: Июнь 22, 2022

The burden of neurological and neuropsychiatric disorders continues to grow with significant impacts on human health social economy worldwide. Increasing clinical preclinical evidences have implicated that bile acids (BAs) are involved in the onset progression diseases. Here, we summarized recent studies BAs three types highly prevalent brain disorders, depression, Alzheimer's disease, stroke. shared specific BA profiles were explored potential markers associated disease development summarized. mechanistic roles reviewed focuses inflammation, gut-brain-microbiota axis, cellular apoptosis. We also discussed future perspectives for prevention treatment by targeting related molecules gut microbiota. Our understanding their is still evolving. A large number questions need be addressed emerging crosstalk among central, peripheral, intestine, contribution mental health.

Язык: Английский

Процитировано

30
Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment DOI

Kyung-Yup Cha,

Woongjin Cho,

Sunghyun Park

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 354, С. 45 - 56

Опубликована: Янв. 3, 2023

Язык: Английский

Процитировано

19
Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice DOI Creative Commons
Junli Ma, Mingxiao Li, Yiyang Bao

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107361 - 107361

Опубликована: Авг. 17, 2024

Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, alterations spatial distribution BAs among different brain regions command important functions during aging and their exact roles aging-related diseases are poorly understood. Here, we analyzed BA profiles cerebral cortex, hippocampus, hypothalamus young natural mice both sexes. The results showed altered sex- region- dependently, which TβMCA was consistently elevated sexes, particularly hippocampus hypothalamus. Furthermore, found accumulated-TβMCA stimulated microglia inflammation vitro shortened lifespan C. elegans, as well behavioral impairment neuroinflammation mice. In addition, metagenomic analysis suggested accumulation partially attributed to reduction BSH-carrying bacteria. Finally, rejuvenation microbiota by co-housing aged with restored homeostasis improved neurological dysfunctions conclusion, our current study highlighted potential improving neuro-impairment targeting microbiota-brain axis.

Язык: Английский

Процитировано

9
Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure DOI

Anfei Liu,

Yunting Li,

Lifan Li

и другие.

Journal of Hazardous Materials, Год журнала: 2024, Номер 471, С. 134360 - 134360

Опубликована: Апрель 19, 2024

Язык: Английский

Процитировано

8
Dysregulated bile acid homeostasis: unveiling its role in metabolic diseases DOI Creative Commons
Yanyan Wang,

Huangru Xu,

Xiqiao Zhou

и другие.

Medical Review, Год журнала: 2024, Номер 4(4), С. 262 - 283

Опубликована: Июнь 3, 2024

Abstract Maintaining bile acid homeostasis is essential for metabolic health. Bile encompasses a complex interplay between biosynthesis, conjugation, secretion, and reabsorption. Beyond their vital role in digestion absorption of lipid-soluble nutrients, acids are pivotal systemic regulation. Recent studies have linked dysregulation to the pathogenesis diseases, including obesity, type 2 diabetes mellitus (T2DM), dysfunction-associated steatotic liver disease (MASLD). signaling molecules that regulate many critical biological processes, lipid metabolism, energy expenditure, insulin sensitivity, glucose metabolism. Disruption contributes via altered feedback mechanisms, hormonal dysregulation, interactions with gut microbiota, changes expression function transporters receptors. This review summarized molecular pathways regulatory mechanisms through which progression T2DM, MASLD. We aim underscore significance as potential diagnostic markers therapeutic agents context providing insights into application translational medicine.

Язык: Английский

Процитировано

8
Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment DOI
Arsh Haj Mohamad Ebrahim Ketabforoush, Faezeh Faghihi, Fereshteh Azedi

и другие.

Clinical Drug Investigation, Год журнала: 2024, Номер 44(7), С. 495 - 512

Опубликована: Июнь 23, 2024

Язык: Английский

Процитировано

8
Molecular mechanism and therapeutic strategy of bile acids in Alzheimer’s disease from the emerging perspective of the microbiota–gut–brain axis DOI Creative Commons
Menglu Wu,

Yongyi Cheng,

Ruolin Zhang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 178, С. 117228 - 117228

Опубликована: Июль 31, 2024

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, endocrinal dysregulation adrenal corticosteroids. These factors collectively contribute to neuronal damage destruction. Recently, bile acids (BAs), which metabolites cholesterol, have shown neuroprotective potential against AD targeting above changes. BAs can enter systematic circulation cross blood–brain barrier, subsequently exerting effects several endogenous receptors. Additionally, interact with microbiota–gut–brain (MGB) axis improve immune neuroendocrine function during episodes. Gut microbes impact BA signaling through their involvement biotransformation. In this review, we summarize role molecular while considering MGB propose novel strategies for preventing onset progression AD.

Язык: Английский

Процитировано

8
Bile acid receptors and signaling crosstalk in the liver, gut and brain DOI Creative Commons
Jessica M. Ferrell, John Y.L. Chiang

Liver Research, Год журнала: 2021, Номер 5(3), С. 105 - 118

Опубликована: Июль 18, 2021

Bile acids are physiological detergents derived from cholesterol that aid in digestion and nutrient absorption, they play roles glucose, lipid, energy metabolism gut microbiome metabolic homeostasis. mediate crosstalk between the liver through bactericidal modulation of microbiome, while microbes influence composition circulating bile acid pool. Recent research indicates may also be important mediators neurological disease by acting as peripheral signaling molecules activate receptors blood-brain barrier brain itself. This review highlights role maintaining microbe homeostasis, well their function cellular liver-gut-brain axis.

Язык: Английский

Процитировано

35