Signaling pathways and targeted therapies for psoriasis

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Language: Английский

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Single-atom catalysts-based catalytic ROS clearance for efficient psoriasis treatment and relapse prevention via restoring ESR1

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 25, 2023

Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which suffered by approximately 3% the world population. The overexpression reactive oxygen species (ROS) plays critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeN4O2-SACs) with broad-spectrum ROS scavenging capability can be used for treatment and relapse prevention via related gene restoration. FeN4O2-SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, are analogous to those natural antioxidant enzymes, superoxide dismutase, human erythrocyte catalase, ascorbate peroxidase. Further, vitro vivo experiments effectively ameliorate psoriasis-like symptoms prevent augmented efficacy compared clinical drug calcipotriol. Mechanistically, estrogen receptor 1 (ESR1) identified as core protein upregulated through RNA sequencing bioinformatic analysis. Together, this study provides proof concept catalytic therapy (PCT) multienzyme-inspired bionics (MIB).

Language: Английский

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The Immunology of Psoriasis—Current Concepts in Pathogenesis

Clinical Reviews in Allergy & Immunology, Journal Year: 2024, Volume and Issue: 66(2), P. 164 - 191

Published: April 20, 2024

Abstract Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades intense research uncovered pathological network interactions between immune cells and other types in pathogenesis psoriasis. Emerging evidence indicates that dendritic cells, T H 17 keratinocytes constitute pathogenic triad Dendritic produce TNF-α IL-23 to promote cell differentiation toward key psoriatic cytokines IL-17, IFN-γ, IL-22. Their activity results inflammation activation hyperproliferation keratinocytes. In addition, signaling pathways are implicated psoriasis, including 9 22 CD8 + cytotoxic neutrophils, γδ chemokines secreted by them. New insights from high-throughput analysis lesional identified novel populations involved pathogenesis. These studies not only expanded our knowledge about mechanisms response psoriasis but also resulted revolution clinical management patients Thus, understanding crucial for further studies, development therapeutic strategies, patients. aim review was comprehensively present dysregulation an emphasis on recent findings. Here, we described role B monocytes, mast innate lymphoid (ILCs), as well non-immune keratinocytes, fibroblasts, endothelial platelets initiation, development, progression

Language: Английский

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Revisiting the interleukin 17 family of cytokines in psoriasis: pathogenesis and potential targets for innovative therapies

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

Published: May 22, 2023

Psoriasis is a common chronic inflammatory skin disease, associated with substantial comorbidity. TH17 lymphocytes, differentiating under the influence of dendritic cell-derived IL-23, and mediating their effects via IL-17A, are believed to be central effector cells in psoriasis. This concept underlined by unprecedented efficacy therapeutics targeting this pathogenetic axis. In recent years, numerous observations made it necessary revisit refine simple “linear” model. It became evident that IL-23 independent exist produce IL-17 homologues may exhibit synergistic biological effects, blockade IL-17A alone clinically less effective compared inhibition several homologues. review, we will summarize current knowledge around its five currently known homologues, namely IL-17B, IL-17C, IL-17D, IL-17E (also as IL-25) IL-17F, relation inflammation general psoriasis particular. We also re-visit above-mentioned integrate them into more comprehensive help appreciate well developing anti-psoriatic therapies prioritize selection future drugs’ mode(s) action.

Language: Английский

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Towards understandings of serine/arginine-rich splicing factors

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(8), P. 3181 - 3207

Published: May 23, 2023

Serine/arginine-rich splicing factors (SRSFs) refer to twelve RNA-binding proteins which regulate splice site recognition and spliceosome assembly during precursor messenger RNA splicing. SRSFs also participate in other metabolic events, such as transcription, translation nonsense-mediated decay, their shuttling between nucleus cytoplasm, making them indispensable for genome diversity cellular activity. Of note, aberrant SRSF expression and/or mutations elicit fallacies gene splicing, leading the generation of pathogenic protein isoforms, highlights therapeutic potential targeting treat diseases. In this review, we updated current understanding structures functions metabolism. Next, analyzed SRSF-induced outcomes cancers non-tumor The development some well-characterized inhibitors was discussed detail. We hope review will contribute future studies drug SRSFs.

Language: Английский

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Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development psoriasis closely related to abnormal activation and disorders the immune system. Dysregulated skin protective mechanisms can activate pathways within epithelial microenvironment (EIME), leading autoimmune-related diseases. In this review, we initially emphasized pathogenesis psoriasis, paying particular attention interactions between cells production cytokines in psoriasis. Subsequently, delved into significance EIME emergence A thorough understanding these processes crucial targeted therapies for Finally, discussed potential novel aimed at modulating This comprehensive examination sheds light on intricate underlying provides insights therapeutic avenues immune-mediated

Language: Английский

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Scarring Skin: Mechanisms and Therapies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1458 - 1458

Published: Jan. 25, 2024

Skin injury always results in fibrotic, non-functional scars adults. Although multiple factors are well-known contributors to scar formation, the precise underlying mechanisms remain elusive. This review aims elucidate intricacies of wound healing process, summarize known driving skin cells wounds toward a scarring fate, and particularly discuss impact fibroblast heterogeneity on formation. To end, we explore potential therapeutic interventions used treatment wounds.

Language: Английский

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DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding

Nature Aging, Journal Year: 2024, Volume and Issue: 4(5), P. 664 - 680

Published: May 17, 2024

Abstract Hyaline cartilage fibrosis is typically considered an end-stage pathology of osteoarthritis (OA), which results in changes to the extracellular matrix. However, mechanism behind this largely unclear. Here, we found that RNA helicase DDX5 was dramatically downregulated during progression OA. deficiency increased phenotype by upregulating COL1 expression and downregulating COL2 expression. In addition, loss aggravated degradation inducing production cartilage-degrading enzymes. Chondrocyte-specific deletion Ddx5 led more severe lesions mouse OA model. Mechanistically, weakened resulted abundance Fn1 -AS-WT Plod2 transcripts, promoted fibrosis-related genes ( Col1 , Acta2 ) matrix Mmp13 Nos2 so on), respectively. Additionally, prevented unfolding Col2 promoter G-quadruplex, thereby reducing production. Together, our data suggest strategies aimed at upregulation hold significant potential for treatment

Language: Английский

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DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(2), P. 770 - 795

Published: Jan. 5, 2024

Abstract DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 METTL14 to form an m6A writing complex, which adds N6-methyladenosine transcripts toll-like receptor (TLR) 2 TLR4, promoting decay via YTHDF2-mediated degradation, resulting reduced expression TLR2/4. Upon bacterial infection, is recruited Hrd1 at the endoplasmic reticulum MyD88-dependent manner degraded by ubiquitin-proteasome pathway. This process disrupts complex halts modification as well degradation TLR2/4 mRNAs, thereby TLR2 TLR4 downstream NF-κB activation. The regulating also validated vivo, DDX5- METTL3-KO mice exhibit enhanced inflammatory cytokines. Our findings show acts a molecular switch regulate during infection shed light on mechanisms quiescent homeostasis.

Language: Английский

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Paradoxical Psoriasis: An Updated Review of Clinical Features, Pathogenesis, and Treatment Options

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(11), P. 2364 - 2376

Published: July 2, 2024

Language: Английский

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