G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 3, 2023

Neuropsychiatric disorders are multifactorial with diverse aetiological factors. Identifying treatment targets is challenging because the diseases resulting from heterogeneous biological, genetic, and environmental Nevertheless, increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge molecular mechanisms structural information GPCRs will be advantageous for developing effective drugs. This review provides an overview role various neurodegenerative psychiatric diseases. Besides, we highlight emerging opportunities novel GPCR address recent progress development.

Язык: Английский

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Inflammation, Dopaminergic Brain and Bilirubin

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11478 - 11478

Опубликована: Июль 14, 2023

Dopamine is a well-known neurotransmitter due to its involvement in Parkinson’s disease (PD). not only involved PD but also controls multiple mental and physical activities, such as the pleasure of food, friends loved ones, music, art, mood, cognition, motivation, fear, affective disorders, addiction, attention deficit disorder, depression, schizophrenia. Dopaminergic neurons (DOPAn) are susceptible stressors, inflammation recognized risk for neuronal malfunctioning cell death major neurodegenerative diseases. Less known non-neurodegenerative conditions. Among endogenous defenses, bilirubin, heme metabolite, has been shown possess important anti-inflammatory activity and, most importantly, prevent DOPAn demise an ex vivo model by acting on tumor necrosis factor-alpha (TNFα). This review summarizes evidence linking DOPAn, (when possible, specifically TNFα), bilirubin order understand what known, gaps that need filling, hypotheses strategies preserve dopamine homeostasis with included.

Язык: Английский

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Dopamine, a co-regulatory component, bridges the central nervous system and the immune system

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 145, С. 112458 - 112458

Опубликована: Ноя. 27, 2021

Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function human body. In the past, most studies focused on relationship between dopaminergic system and neurological-related diseases. However, it has been found recently DA immunomodulatory mediator many immune cells express dopamine receptors (DRs). Some can synthesize secrete then participate regulating function. DRs agonists or antagonists improve dysfunction of through classical G protein signaling pathways other non-receptor-dependent pathways. This article will discuss system. It also review use to treat chronic acute inflammatory diseases corresponding mechanisms.

Язык: Английский

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Psychoses onset in multiple sclerosis: A systematic review and meta-analysis

Revue Neurologique, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Potential Metabolite Biomarkers of Multiple Sclerosis from Multiple Biofluids

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(6), С. 1110 - 1124

Опубликована: Фев. 29, 2024

Multiple sclerosis (MS) is a chronic and progressive neurological disorder without cure, but early intervention can slow disease progression improve the quality of life for MS patients. Obtaining an accurate diagnosis arduous error-prone task that requires combination detailed medical history, comprehensive exam, clinical tests such as magnetic resonance imaging, exclusion other possible diseases. A simple definitive biofluid test does not exist, highly desirable. To address this need, we employed NMR-based metabolomics to identify potentially unique metabolite biomarkers from cohort age sex-matched samples cerebrospinal fluid (CSF), serum, urine 206 (PMS) patients, 46 relapsing-remitting (RRMS) 99 healthy volunteers diagnosis. We identified 32 metabolites in CSF varied between control PMS Utilizing patient-matched serum samples, were able further 31 may serve Lastly, 14 associated with PMS. All potential are metabolic processes linked pathology MS, demyelination neuronal damage. Four identical profiles across all three biofluids discovered, which demonstrate their value cross-biofluid markers present case using patients delineate RRMS. Specifically, exhibited variation through RRMS The consistency changes multiple biofluids, combined reliability receiver operating characteristic classification, provide rapid diagnostic MS.

Язык: Английский

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Defining a vitamin A5/X specific deficiency – vitamin A5/X as a critical dietary factor for mental health

International Journal for Vitamin and Nutrition Research, Год журнала: 2024, Номер 94(5-6), С. 443 - 475

Опубликована: Июнь 1, 2024

A healthy and balanced diet is an important factor to assure a good functioning of the central peripheral nervous system. Retinoid X receptor (RXR)-mediated signaling was identified as mechanism transmitting major diet-dependent physiological nutritional such control myelination dopamine signalling. Recently, vitamin A5/X, mainly present in vegetables provitamin new concept which functions precursor for enabling RXR-mediated signaling. The active form 9-

Язык: Английский

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In Silico Drug Repurposing in Multiple Sclerosis Using scRNA-Seq Data

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 985 - 985

Опубликована: Янв. 4, 2023

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system still lacking a cure. Treatment typically focuses on slowing progression and managing MS symptoms. Single-cell transcriptomics allows investigation immune system-the key player in onset development-in great detail increasing our understanding mechanisms stimulating discovery targets for potential therapies. Still, de novo drug development takes decades; however, this can be reduced by repositioning. A promising approach to select drugs based activated or inhibited genes pathways. In study, we explored public single-cell RNA data from experiment with six patients peripheral blood mononuclear cells (PBMC) cerebrospinal fluid (CSF) idiopathic intracranial hypertension. We demonstrate that AIM2 inflammasome, SMAD2/3 signaling, complement activation pathways are different CSF PBMC cells. Using top-activated pathways, detected several small molecules reverse cells' transcriptomic signatures, including AG14361, FGIN-1-27, CA-074, ARP 101, Flunisolide, JAK3 Inhibitor VI. Among these molecules, also FDA-approved Mitoxantrone, supporting reliability approach.

Язык: Английский

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Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, Год журнала: 2024, Номер 23(2), С. 138 - 147

Опубликована: Апрель 3, 2024

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate process. Calcitriol, active form of vitamin D, curcumin, bioactive compound derived from turmeric, play immunomodulatory effects relevant to disorders, including MS. The objective this study investigate calcitriol Curcumin on Peripheral blood mononuclear (PBMCs) individuals with

Язык: Английский

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Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Янв. 4, 2024

Abstract Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting complex nature manifestations. With aim explaining symptoms related to central nervous system, we utilized a rat model investigate impact dopamine signaling in peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, flow cytometry. In this study, observed increased activated both system circulation myasthenia rats. Furthermore, changes expression two key molecules, Claudin5 CD31, endothelial cells blood–brain barrier were examined these confirmed incubation reduced ZO1, Claudin5, CD31 inhibiting Wnt/β-catenin pathway. Overall, study provides novel evidence pathologically elevated rats impair brain–blood integrity junction protein brain microvascular through Graphical

Язык: Английский

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Altered Steroidome in Women with Multiple Sclerosis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12033 - 12033

Опубликована: Ноя. 8, 2024

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence onset and development or, on contrary, mitigate its course; however, systematic review steroidomic changes in MS patients lacking. Based gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, case estradiol, also using immunoassay, this study performed comprehensive analysis 25 female aged 39(32, 49) years compared to 15 age-matched controls 38(31, 46) years. A significant trend towards higher ratios conjugated their unconjugated counterparts was found patients, which particular interest terms balance between excitatory inhibitory steroid modulators ionotropic receptors. Patients showed altered metabolic pathway cortisol with decreased conversion pregnenolone 17-hydroxypregnenolone 17-hydroxyprogesterone increased dehydroepiandrosterone (DHEA), resulting lower levels 17-hydroxyprogesterone, as well indications impaired 11-deoxy-steroids 11β-hydroxy-steroids but reduced cortisone. Due over-activation hypothalamic-pituitary-adrenal axis (HPAA), cortisone were depleted synthesizing enzymes. DHEA androstenedione, androstenedione testosterone, estradiol major pathway, testosterone minor for synthesis at testosterone. They immunoprotective Δ

Язык: Английский

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