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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Dendritic Cells and Macrophages in the Pathogenesis of Psoriasis

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

Published: June 28, 2022

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. This impairs patients’ quality of life enormously. Pathological findings demonstrate proliferation and abnormal differentiation keratinocytes massive infiltration immune cells. The pathogenesis psoriasis complicated. Among cells, dendritic cells play pivotal role in the development both initiation maintenance phases. In addition, it has been indicated that macrophages contribute to especially phase, although studies on are limited. this article, we review roles psoriasis.

Language: Английский

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Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches for Prolonged and Intelligent Psoriasis Management

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4346 - 4357

Published: Feb. 27, 2023

Psoriasis is an inflammatory skin disease. Microneedle (MN) patches can improve psoriasis treatment outcomes by increasing local drug content in the skin. As frequently relapses, developing intelligent MN-based delivery systems with prolonged therapeutic levels and improved efficiency of great significance. Here, we designed detachable H2O2-responsive gel-based MN containing methotrexate (MTX) epigallocatechin gallate (EGCG) using EGCG as both cross-linkers for needle-composited materials anti-inflammatory drugs. The MNs had dual-mode release kinetics, which quickly released MTX diffusively sustainably way. Compared dissolving MNs, extended retention EGCG, leading to reactive oxygen species (ROS) scavenging effects. ROS-responsive that transdermally delivered antiproliferative drugs psoriasis-like prophylactic animal models.

Language: Английский

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Psoriatic Arthritis: Pathogenesis and Targeted Therapies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4901 - 4901

Published: March 3, 2023

Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated uveitis bowel (Crohn’s ulcerative colitis). To capture these manifestations as well the comorbidities, to recognize their underlining common pathogenesis, name of psoriatic was coined. The pathogenesis complex multifaceted, an interplay genetic predisposition, triggering environmental factors, activation innate adaptive immune system, although autoinflammation has been implicated. Research identified several immune-inflammatory pathways defined cytokines (IL-23/IL-17, TNF), leading development efficacious therapeutic targets. However, responses drugs occur different tissues involved, resulting challenge global management disease. Therefore, more translational research necessary order identify new targets improve current outcomes. Hopefully, this may become reality through integration omics technologies that allow better understanding relevant cellular molecular players In narrative review, we aim provide updated overview pathophysiology, including latest findings from multiomics studies, describe targeted therapies.

Language: Английский

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Comprehensive Insight into Lichen Planus Immunopathogenesis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3038 - 3038

Published: Feb. 3, 2023

Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen rare occurring in less than 1% of general population, while oral illness up to five times more prevalent; still, both forms equally impair patient’s quality life. The etiology not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger genetically susceptible individuals. According current understanding, immunopathogenesis caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity further influenced Th1 IL-23/Th-17 axis. However, other immunocytes inflammatory pathways complement these mechanisms. This paper presents comprehensive insight into actual knowledge about planus, with causal genetic being discussed, described, principal effectors its circuits identified.

Language: Английский

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Updated Perspectives on Keratinocytes and Psoriasis: Keratinocytes are More Than Innocent Bystanders

Psoriasis Targets and Therapy, Journal Year: 2022, Volume and Issue: Volume 12, P. 73 - 87

Published: May 1, 2022

Psoriasis is a complex disease triggered by genetic, immunologic, and environmental stimuli. Many genes have been linked to psoriasis, like the psoriasis susceptibility genes, some of which are critical in keratinocyte biology epidermal barrier function. Still, exact pathogenesis unknown. In disease, balance between proliferative differentiative processes keratinocytes becomes altered. Multiple studies highlighted role dysregulated immune cells provoking inflammatory responses seen psoriasis. addition cells, accumulating evidence shows that involved pathogenesis, as discussed this review. Although certain cell-derived factors stimulate hyperproliferation, activated can also produce anti-microbial peptides, cytokines, chemokines promote their proliferation, well recruit help initiate reinforce feedback loops. Psoriatic show intrinsic differences from normal even after removal vivo environment; thus, psoriatic found exhibit abnormal calcium metabolism possible epigenetic changes contribute The Koebner phenomenon, injury promotes development lesions, provides for keratinocytes' contributions pathogenesis. Furthermore, transgenic mouse confirmed importance etiology Finally, keratinocytes, data literature support roles other cell types, tissues, systems development. These contributors all potential targets therapies, suggesting holistic approach when treating

Language: Английский

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Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8575 - 8575

Published: Aug. 2, 2022

Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology psoriasis are still unknown, but activation adaptive immune system with main role T-cells key in pathogenesis. modulation local neuroendocrine downregulation pro-inflammatory upregulation anti-inflammatory messengers represent promising adjuvant treatment therapies. Vitamin D receptors vitamin D-mediated signaling pathways function skin essential maintaining homeostasis. active forms act as powerful immunomodulators clinical response psoriatic patients effective safe treatments for psoriasis, even when high doses administered. phototherapy especially UVB-based, changes serum level 25(OH)D, correlation 25(OH)D improvement need more trials, since contradictory data have been published. derivatives can improve efficacy without inducing adverse side effects. anti-psoriatic could include non-calcemic CYP11A1-derived hydroxyderivatives would on VDR or inverse agonists RORs activate alternative nuclear including AhR LXRs. In conclusion, play an important natural history psoriasis. Selective targeting proper potential options

Language: Английский

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The holistic approach to psoriasis patients with comorbidities: the role of investigational drugs

Expert Opinion on Investigational Drugs, Journal Year: 2023, Volume and Issue: 32(6), P. 537 - 552

Published: May 27, 2023

Introduction Psoriasis is a high-burden syndrome characterized by cutaneous and extracutaneous manifestations that profoundly reduce patients’ quality of life. The presence concomitant comorbidities often represents limit to the most appropriate psoriasis treatment will be overcome development drugs effective for diseases with common pathogenetic pathways.

Language: Английский

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TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases

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

Published: Feb. 15, 2023

TRPV1 is a non-selective channel receptor widely expressed in skin tissues, including keratinocytes, peripheral sensory nerve fibers and immune cells. It activated by variety of exogenous or endogenous inflammatory mediators, triggering neuropeptide release neurogenic response. Previous studies have shown that closely related to the occurrence and/or development aging various chronic diseases, such as psoriasis, atopic dermatitis, rosacea, herpes zoster, allergic contact dermatitis prurigo nodularis. This review summarizes structure discusses expression well its role diseases.

Language: Английский

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The Skin Microbiome and Its Role in Psoriasis: A Review

Psoriasis Targets and Therapy, Journal Year: 2023, Volume and Issue: Volume 13, P. 71 - 78

Published: Oct. 1, 2023

The skin microbiome is made of various microorganisms, most which have the function protecting individuals from harmful pathogens, and they are involved in innate adaptive immune responses. acts as a physical immunological barrier against external stimuli, including pathogens damage. Changes composition can trigger inflammatory processes leading to diseases susceptible individuals. Psoriasis (PsO) chronic disease with multifactorial etiology, where breakdown tolerance cutaneous microorganisms implicated its pathogenesis. Dysregulation due genetic environmental factors plays significant role development psoriatic disease. Dermatologic conditions such atopic dermatitis, acne, psoriasis, rosacea been associated intestinal dysbiosis. microbiota crucial for appropriate responses, alterations contribute changes physiology susceptibility or conditions. Understanding microbial settlement network interactions that occur throughout life essential comprehending pathogenesis developing innovative treatments. With this article we tried explore relationship between human disease, shedding light on functions identify additional therapeutic targets. This review aims highlight gut psoriasis arthritis (PsA). goal facilitate future studies potential novel therapies patients

Language: Английский

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