Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 905 - 905

Опубликована: Янв. 14, 2022

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and complications. Currently, advanced understandings of the pathologic mechanisms autoreactive CD4+ T cells, B macrophages, inflammatory cytokines, chemokines, autoantibodies that cause RA have been achieved, despite fact much remains to be elucidated. This review provides an updated pathogenesis which will unveil novel therapeutic targets.

Язык: Английский

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Signaling pathways in rheumatoid arthritis: implications for targeted therapy

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

Опубликована: Фев. 17, 2023

Abstract Rheumatoid arthritis (RA) is an incurable systemic autoimmune disease. Disease progression leads to joint deformity and associated loss of function, which significantly impacts the quality life for sufferers adds losses in labor force. In past few decades, RA has attracted increased attention from researchers, abnormal signaling pathways are a very important research field diagnosis treatment RA, provides evidence understanding this complex disease developing novel RA-linked intervention targets. The current review intends provide comprehensive overview including general introduction disease, historical events, epidemiology, risk factors, pathological process, highlight primary progress various molecular mechanisms, genetic epigenetic summarize most recent developments identifying new inhibitors treating RA. therapeutic interventions approved drugs, clinical pre-clinical cutting-edge technologies. These will hopefully drive strategically targeted therapies hope ideas options future.

Язык: Английский

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B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Сен. 28, 2021

Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, formation pannus destruction cartilage. The global incidence RA about 1%, it more common in women. basic feature body’s immune system disorders, which autoreactive CD4 + T cells, pathogenic B M1 macrophages, inflammatory cytokines, chemokines autoantibodies abnormally increase body patients cell depletion therapy has well proved important role cells pathogenesis RA, treatment with as target also been paid attention. Although indicators receiving B-cell have significantly improved, risk infection cancer increased, suggests that we need to deplete instead all cells. However, at present cannot distinguish between protective patients. In this review, explore fresh perspectives upon roles occurrence, development RA.

Язык: Английский

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Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

European Journal of Medicinal Chemistry, Год журнала: 2020, Номер 210, С. 112981 - 112981

Опубликована: Окт. 31, 2020

Язык: Английский

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Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial

The Lancet Neurology, Год журнала: 2021, Номер 20(9), С. 729 - 738

Опубликована: Авг. 19, 2021

Язык: Английский

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Phosphorylation-Inducing Chimeric Small Molecules

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(33), С. 14052 - 14057

Опубликована: Авг. 4, 2020

Small molecules have been classically developed to inhibit enzyme activity; however, new classes of small that endow functions enzymes via proximity-mediated effect are emerging. Phosphorylation (native or neo) any given protein-of-interest can alter its structure and function, we hypothesized such modifications be accomplished by bring a kinase in proximity the protein-of-interest. Herein, describe phosphorylation-inducing chimeric (PHICS), which enable two example kinases—AMPK PKC—to phosphorylate target proteins not otherwise substrates for these kinases. PHICS formed linking small-molecule binders protein, exhibit several features bifunctional molecule, including hook-effect, turnover, isoform specificity, dose temporal control phosphorylation, activity dependent on (i.e., linker length). Using PHICS, were able induce native neo-phosphorylations BRD4 AMPK PKC. Furthermore, induced signaling-relevant phosphorylation protein Bruton's tyrosine cells. We envision PHICS-mediated will find utility basic research medicine.

Язык: Английский

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Bruton tyrosine kinase inhibitors for multiple sclerosis

Nature Reviews Neurology, Год журнала: 2023, Номер 19(5), С. 289 - 304

Опубликована: Апрель 13, 2023

Язык: Английский

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Updates and Advances in Multiple Sclerosis Neurotherapeutics

Neurodegenerative Disease Management, Год журнала: 2022, Номер 13(1), С. 47 - 70

Опубликована: Окт. 31, 2022

The multiple sclerosis (MS) neurotherapeutic landscape is rapidly evolving. New disease-modifying therapies (DMTs) with improved efficacy and safety, in addition to an expanding pipeline of agents novel mechanisms, provide more options for patients MS. While treatment MS neuroinflammation well tailored the existing DMT armamentarium, concerted efforts are currently underway identifying neuropathological targets drug discovery progressive There also ongoing research develop remyelination neuroprotection. Further insights needed guide initiation sequencing as determine role autologous stem cell transplantation relapsing This review provides a summary these updates.

Язык: Английский

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Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria

Journal of Allergy and Clinical Immunology, Год журнала: 2022, Номер 150(6), С. 1498 - 1506.e2

Опубликована: Сен. 9, 2022

Chronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective CSU.This first-in-patient trial aimed to evaluate the efficacy safety remibrutinib CSU treatment characterize dose-response.This randomized, double-blind, placebo-controlled, phase 2b dose-finding evaluated (12 weeks) with second-generation H1-antihistamines, at least moderately active CSU, or without prior anti-IgE (NCT03926611). Patients received 10 mg once daily, 35 100 twice 25 placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline week 4 safety.Overall, 311 randomized. Reduced symptom score was observed for all doses 1 until 12, 4: -19.1 (10 daily), (35 -14.7 (100 -16.0 -20.0 (25 -18.1 -5.4 (nominal P < .0001 vs placebo). Most adverse events mild moderate, no dose-dependent pattern.Remibrutinib over entire dose range, rapid onset action favorable profile.

Язык: Английский

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Anti-CD20 therapies for multiple sclerosis: current status and future perspectives

Journal of Neurology, Год журнала: 2021, Номер 269(3), С. 1316 - 1334

Опубликована: Авг. 11, 2021

Язык: Английский

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