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

The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets DOI Creative Commons
Millicent N. Ekwudo, Carolina Gubert, Anthony J. Hannan

и другие.

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Март 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Язык: Английский

Процитировано

23
Increased intestinal bile acid absorption contributes to age-related cognitive impairment DOI Creative Commons
Zhenxing Ren, Ling Zhao,

Mingliang Zhao

и другие.

Cell Reports Medicine, Год журнала: 2024, Номер 5(5), С. 101543 - 101543

Опубликована: Май 1, 2024

Cognitive impairment in the elderly is associated with alterations bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary acids (CPBAs) and ammonia individuals, mild cognitive impairment, Alzheimer's disease, aging rodents, a more pronounced change females. These changes are correlated increased expression ileal apical sodium-bile transporter (ASBT), hippocampal synapse loss, brain CPBA rodents. vitro experiments confirm that CPBA, taurocholic acid, induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates impact on as well decline Additionally, administration an sequestrant, cholestyramine, alleviates normalizing CPBAs mice. findings highlight potential targeting absorption therapeutic strategy for age-related impairment.

Язык: Английский

Процитировано

18
From dried bear bile to molecular investigation: A systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders DOI
Fei Huang, Carmine M. Pariante, Alessandra Borsini

и другие.

Brain Behavior and Immunity, Год журнала: 2021, Номер 99, С. 132 - 146

Опубликована: Сен. 30, 2021

Язык: Английский

Процитировано

78
Bile Acids as Key Modulators of the Brain-Gut-Microbiota Axis in Alzheimer’s Disease DOI Creative Commons
Agata Mulak

Journal of Alzheimer s Disease, Год журнала: 2021, Номер 84(2), С. 461 - 477

Опубликована: Сен. 24, 2021

Recently, the concept of brain-gut-microbiota (BGM) axis disturbances in pathogenesis Alzheimer’s disease (AD) has been receiving growing attention. At same time, accumulating data revealing complex interplay between bile acids (BAs), gut microbiota, and host metabolism have shed new light on a potential impact BAs BGM axis. The crosstalk microbiota is based reciprocal interactions since determines BA metabolism, while affect composition. Secondary as microbe-derived neuroactive molecules may each three main routes through which within occur including neural, immune, neuroendocrine pathways. participate regulation multiple gut-derived molecule release their receptors are expressed various cells. presence brain implies direct effect neurological functions. Experimental clinical confirm that signaling present course AD. Disturbed ratio primary to secondary well alterations concertation serum samples reported. An age-related shift composition associated with its decreased diversity stability observed AD patients significantly signaling. Given recent evidence neuroprotective anti-inflammatory effects, therapeutic targets explored modulation by probiotics dietary interventions, ursodeoxycholic acid supplementation, use receptor agonists.

Язык: Английский

Процитировано

71
Targeting Microglia to Treat Degenerative Eye Diseases DOI Creative Commons
Sean K. Wang, Constance L. Cepko

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 17, 2022

Microglia have been implicated in many degenerative eye disorders, including retinitis pigmentosa, age-related macular degeneration, glaucoma, diabetic retinopathy, uveitis, and retinal detachment. While the exact roles of microglia these conditions are still being discovered, evidence from animal models suggests that they can modulate course disease. In this review, we highlight current strategies to target their potential as treatments for both rare common ocular disorders. These approaches include depleting with chemicals or radiation, reprogramming using homeostatic signals other small molecules, inhibiting downstream effects such by blocking cytokine activity phagocytosis. Finally, describe areas future research needed fully exploit therapeutic value diseases.

Язык: Английский

Процитировано

46
Bile acids and neurological disease DOI Creative Commons
Michael J. Hurley, Rachel Bates, Jane Macnaughtan

и другие.

Pharmacology & Therapeutics, Год журнала: 2022, Номер 240, С. 108311 - 108311

Опубликована: Ноя. 16, 2022

This review will focus on how bile acids are being used in clinical trials to treat neurological diseases due their central involvement with the gut-liver-brain axis and physiological pathophysiological roles both normal brain function multiple diseases. The synthesis of primary secondary species regulation acid pool may differ between gut is discussed. expression several receptors currently known functions along tools available manipulate them pharmacologically examined, together discussion interaction microbiome lesser-known effects upon glucose lipid metabolism. How dysregulation microbiome, aging sex differences lead disruption signalling possible causal a number disorders also considered. Finally, we discuss pharmacological treatments targeting tested an array for different neurodegenerative

Язык: Английский

Процитировано

44
Cell Rearrangement and Oxidant/Antioxidant Imbalance in Huntington’s Disease DOI Creative Commons
Francesco D’Egidio, Vanessa Castelli, Annamaria Cimini

и другие.

Antioxidants, Год журнала: 2023, Номер 12(3), С. 571 - 571

Опубликована: Фев. 24, 2023

Huntington’s Disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of CAG triplet repeat in HTT gene, resulting production an aberrant huntingtin (Htt) protein. The mutant protein accumulation responsible for neuronal dysfunction and cell death. This due to involvement oxidative damage, excitotoxicity, inflammation, mitochondrial impairment. Neurons naturally adapt bioenergetic alteration stress physiological conditions. However, this dynamic system compromised when occurs, changes metabolism, calcium signaling, impaired substrates transport. Thus, aim review provide overview cell’s answer induced HD, focusing on role its balance with antioxidant system.

Язык: Английский

Процитировано

29
Connecting the Gut Microbiota and Neurodegenerative Diseases: the Role of Bile Acids DOI

Shixu Wang,

Chongchong Xu, Hongyan Liu

и другие.

Molecular Neurobiology, Год журнала: 2023, Номер 60(8), С. 4618 - 4640

Опубликована: Май 1, 2023

Язык: Английский

Процитировано

24
Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics DOI Creative Commons
Yaxi Luo,

Ling-Ling Yang,

Xiu‐Qing Yao

и другие.

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Апрель 16, 2024

Abstract Trillions of intestinal bacteria in the human body undergo dynamic transformations response to physiological and pathological changes. Alterations their composition metabolites collectively contribute progression Alzheimer’s disease. The role gut microbiota disease is diverse complex, evidence suggests lipid metabolism may be one potential pathways. However, mechanisms that mediate pathology remain unclear, necessitating further investigation for clarification. This review highlights current understanding how disrupts discusses implications these discoveries guiding strategies prevention or treatment based on existing data.

Язык: Английский

Процитировано

15
Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease DOI Creative Commons

Honghu Song,

Jiancheng Liu, Linjie Wang

и другие.

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 19, 2024

Alzheimer’s disease (AD) is a prevalent neurodegenerative that has become one of the main factors affecting human health. It serious impacts on individuals, families, and society. With development population aging, incidence AD will further increase worldwide. Emerging evidence suggests many physiological metabolic processes, such as lipid metabolism, are implicated in pathogenesis AD. Bile acids, undertakers play an important role occurrence disease. Tauroursodeoxycholic acid, endogenous bile been proven to possess therapeutic effects different diseases, including This review tries find relationship between acid metabolism AD, well explore potential taurocursodeoxycholic for this The mechanisms may include reducing deposition Amyloid-β protein, regulating apoptotic pathways, preventing tau hyperphosphorylation aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, improving disorders. objective study shed light use tauroursodeoxycholic preparations prevention treatment with aim identifying effective targets clarifying various involved

Язык: Английский

Процитировано

12