Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction myelin sheath structure. The loss leads to damage neuron’s axon and cell body, which identified as brain lesions on magnetic resonance image (MRI). pathogenesis MS remains largely unknown. However, immune mechanisms, especially those linked aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 Th17 populations lymphocytes were primarily associated with pathogenesis. These essential differentiation encephalitogenic CD8 + T crossing blood barrier targeting in CNS. B-lymphocytes could also contribute producing anti-myelin basic protein antibodies. In later studies, function Treg Th9 cells was contributing MS. This review summarizes count lymphocyte, contributions these mechanisms Additionally, we have outlined novel therapeutics aimed amend or counts lymphocytes.

Language: Английский

---

Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The exists as either transmembrane or soluble molecule, and targets two distinct receptors, TNF-α 1 (TNFR1) 2 (TNFR2), which activate different signaling cascades downstream genes. cellular responses depend on its molecular form, targeted receptor, concentration levels. plays multifaceted role in normal physiology highly relevant human health disease. In central nervous system (CNS), this regulates homeostatic functions, such neurogenesis, myelination, blood-brain barrier permeability synaptic plasticity. However, it can also potentiate neuronal excitotoxicity CNS inflammation. pleiotropism various roles CNS, whether deleterious, only emphasizes functional complexity cytokine. Anti-TNF-α therapy has demonstrated effectiveness treating autoimmune inflammatory diseases emerged significant treatment option for diseases. Nevertheless, crucial recognize effects therapeutic target are diverse complex. Contrary initial expectations, anti-TNF-α been found have detrimental multiple sclerosis. This article focuses describing roles, both physiological pathological, CNS. Additionally, discusses specific disease processes dependent regulated by rationale use target.

Language: Английский

---

Exploring TNFR1: from discovery to targeted therapy development

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 15, 2025

Language: Английский

---

Psoriasis as an Immune-Mediated and Inflammatory Systemic Disease: From Pathophysiology to Novel Therapeutic Approaches

Biomedicines, Journal Year: 2021, Volume and Issue: 9(11), P. 1511 - 1511

Published: Oct. 21, 2021

Psoriasis is an immune-mediated inflammatory disease, with a chronic relapsing-remitting course, which affects 2-3% of the worldwide population. The progressive acquisitions pathways involved in development psoriasis have led to identification key molecules psoriatic cascade. At same time, therapy has radically evolved introduction target able modify natural history acting specifically on these pathways. For reasons, biologics been demonstrated be drugs change disease's history, as they reduce background avoid irreversible organ damage and prevent systemic complications. However, several issues related use patients comorbidities, remain open. All data reflect extraordinary potentiality biologics, but also unmet medical need improve our knowledge long-term risk continuous drugs, their administration special populations. This narrative review aims highlight both efficacy safety profile psoriasis, starting from pathophysiology moving towards clinical application.

Language: Английский

---

Multi-omic evaluation of metabolic alterations in multiple sclerosis identifies shifts in aromatic amino acid metabolism

Cell Reports Medicine, Journal Year: 2021, Volume and Issue: 2(10), P. 100424 - 100424

Published: Oct. 1, 2021

The circulating metabolome provides unique insights into multiple sclerosis (MS) pathophysiology, but existing studies are relatively small or characterized limited metabolites. We test for differences in the between people with MS (PwMS; n = 637 samples) and healthy controls (HC; 317 assess association metabolomic profiles disability PwMS. then whether metabolic correlate changes cellular gene expression using publicly available scRNA-seq data identified metabolites affect human immune cell function. In PwMS, we identify striking abnormalities aromatic amino acid (AAA) (p 2.77E-18) that also strongly associated 1.01E-4). Analysis of demonstrates altered AAA metabolism CSF blood-derived monocyte populations Treatment AAA-derived vitro alters monocytic endocytosis pro-inflammatory cytokine production. shifts resulting reduced production immunomodulatory increased metabotoxins

Language: Английский

---

NF-κB Signaling and Inflammation—Drug Repurposing to Treat Inflammatory Disorders?

Biology, Journal Year: 2022, Volume and Issue: 11(3), P. 372 - 372

Published: Feb. 26, 2022

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As result its role in so many important cellular processes, dysregulation has been implicated the pathology human diseases. activation causes inappropriate inflammatory responses diseases including rheumatoid arthritis (RA) multiple sclerosis (MS). Thus, modulation signaling being widely investigated as an approach treat chronic diseases, autoimmunity cancer. The emergence COVID-19 late 2019, subsequent pandemic huge clinical burden patients with life-threatening SARS-CoV-2 pneumonia led massive scramble repurpose existing medicines lung inflammation wide range healthcare systems. These efforts continue have proven be controversial. Drug repurposing strategies are promising alternative de novo drug development, they minimize development timelines reduce risk failure due unexpected side effects. Different experimental approaches applied identify which inhibit that could repurposed anti-inflammatory drugs.

Language: Английский

---

ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(5), P. 815 - 853

Published: March 27, 2023

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit delivery of drugs into brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem successfully treat CNS diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical solve this problem. In comprehensive review, we summarize current knowledge on signaling pathways regulate barrier. part I, give historical overview research introduce role play in context. II, most important strategies tested system III, main component provide detailed information identified their potential relevance. This followed by IV, where explain implications context disease. Lastly, V, conclude highlighting examples how could be targeted for therapeutic purposes clinic. Significance Statement significant successful Here, review potentially purposes.

Language: Английский

---

The Role of TNF-α in Alzheimer’s Disease: A Narrative Review

Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 54 - 54

Published: Dec. 26, 2023

This review analyzes the role of TNF-α and its increase in biological fluids mild cognitive impairment, Alzheimer’s disease (AD). The potential inhibition with pharmacological strategies paves way for preventing AD improving function people at risk dementia. We conducted a narrative to characterize evidence relation involvement possible therapeutic inhibition. Several studies report that patients RA systemic inflammatory diseases treated blocking agents reduce probability emerging dementia compared general population. Animal model also showed interesting results are discussed. An increasing amount basic scientific data clinical underscore importance processes subsequent glial activation pathogenesis AD. targeted therapy is biologically plausible approach cognition preservation further trials necessary investigate benefits populations developing

Language: Английский

---

Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications

Neuroscience, Journal Year: 2024, Volume and Issue: 548, P. 9 - 26

Published: April 30, 2024

Language: Английский

---

Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---