Insight into the pivotal role of signaling pathways in psoriasis pathogenesis, potential therapeutic molecules and drug delivery approaches

Tomar, Yashika; Gorantla, Srividya; Singhvi, Gautam

doi:10.1016/j.drudis.2022.103465

Cited by 18 publications

(7 citation statements)

References 65 publications

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“…mRNA surveillance is a quality control physiological mechanism, and moreover, the osteoarticular involvement in psoriasis could be mediated by an abnormal immunologic process mediated by the mRNA surveillance pathway (Navickas et al 2020;Zhang et al 2022b). The activation of the NF-κB pathway can lead to increased transcription of numerous genes involved in the onset and perpetuation of the in ammatory response in psoriasis Tomar et al 2023). Hypomethylated DMGs in psoriasis were mainly related to neural regulation (axon guidance, endocytosis) as well as the Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of crucial m6A-related differentially expressed genes associated with psoriasis

Gan

Xuejingzi

Song

2023

Preprint

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Psoriasis is a chronic inflammatory skin disease that involves genetic and epigenetic factors. N6-methyladenosine methylation (m6A) is the most prevalent RNA modification implicated in various diseases; however, its role in psoriasis remains unclear. Three psoriasis-related datasets were collected from the Gene Expression Omnibus (GEO) database. Differentially m6A methylated genes (DMGs) between psoriasis and controls were identified from the GSE155702 dataset, and corresponding GO and KEGG pathway analyses were performed. Differentially expressed genes (DEGs) and the common DEGs between these two groups were screened from the GSE109248 and GSE142582 datasets. The gene expression of m6A methylation regulators and the interactions among these regulators were also analyzed. 66 significantly upregulated and 381 significantly downregulated m6A peaks were identified corresponding to 414 genes, which were particularly associated with cell and tissue development processes and cell cycle-related items. 271 common DEGs were identified, associating with keratinocyte differentiation, epidermis development, cytokine-cytokine receptor interaction, and fatty acid metabolic processes. 15 crucial m6A-related differentially expressed genes were obtained after the intersection of the DMGs and common DEGs, including NEU2, GALNT6, MTCL1, DOC2B, CAMK2N1, SNTB1, RNF150, CGNL1, CCDC102A, MEOX2, EEF2K, OBSCN, SLC46A2, CCDC85A and DACH1. Our research revealed that psoriasis pathophysiological processes encompass m6A epigenetic alterations, and that m6A alterations may specifically influence cell proliferation and neural regulation and closely associated with osteoarticular involvement and metabolic syndrome in psoriasis.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of crucial m6A-related differentially expressed genes associated with psoriasis

Gan

Xuejingzi

Song

2023

Preprint

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“…The intracellular concentration of cAMP is linked to pro-inflammatory intracellular signaling, making PDE a pivotal molecule in inflammatory diseases such as psoriasis ( 259 ). The FDA has approved two PDE-4 inhibitors: the oral formulation of apremilast and the topical cream of roflumilast ( 260 , 261 ). Several experimental and clinical studies have demonstrated the efficacy and tolerability of these two agents in psoriasis treatment.…”

Section: Emerging Therapies Targeting Immune Cells In Psoriasismentioning

confidence: 99%

“…Another approach to target the pathogenesis of psoriasis involves JAK inhibitors. JAK1, JAK2, and tyrosine kinase 2(TYK2)are key enzymes implicated in psoriasis, and JAK inhibitors reduce the transcription of pro-inflammatory cytokines by blocking the JAK-STAT pathway ( 260 ). Selective TYK2 inhibitor BMS-986165 has shown promising results in phase II clinical data, while PF-06826647 is currently undergoing phase II clinical trials.…”

Section: Emerging Therapies Targeting Immune Cells In Psoriasismentioning

confidence: 99%

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

Li,

Lu,

Liu

et al. 2024

Front. Immunol.

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

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“…It is a chronic autoimmune disorder with scaly lesions on the skin exhibiting characteristics of a typical inflammatory reaction: stinging sensation, pain, and bleeding. Chronic plaque psoriasis, the most prevalent form, is caused by a combined play of both genetic predisposition and environmental triggers including stress, damage, infections, etc. , In research by Mart et al, three compounds (capsaicin, salicylic acid, and methyl salicylate) were utilized in the fabrication of nanofibers of poly(methyl vinyl ether- alt -maleic ethyl monoester) (PMVEMA-ES) for the treatment of psoriasis dermal symptoms. With respect to the amount of polymer, 3.5% w/w concentration of the active constituents was loaded with 100% encapsulation efficiency.…”

Section: Therapeutic Applications Of Nanofibersmentioning

confidence: 99%

Evolving Trends in Nanofibers for Topical Delivery of Therapeutics in Skin Disorders

Tomar,

Pandit,

Priya

et al. 2023

ACS Omega

Self Cite

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Nanotechnology has yielded nanostructure-based drug delivery approaches, among which nanofibers have been explored and researched for the potential topical delivery of therapeutics. Nanofibers are filaments or thread-like structures in the nanometer size range that are fabricated using various polymers, such as natural or synthetic polymers or their combination. The size or diameter of the nanofibers depends upon the polymers, the techniques of preparation, and the design specification. The four major processing techniques, phase separation, self-assembly, template synthesis, and electrospinning, are most commonly used for the fabrication of nanofibers. Nanofibers have a unique structure that needs a multimethod approach to study their morphology and characterization parameters. They are gaining attention as drug delivery carriers, and the substantially vast surface area of the skin makes it a potentially promising strategy for topical drug products for various skin disorders such as psoriasis, skin cancers, skin wounds, bacterial and fungal infections, etc. However, the large-scale production of nanofibers with desired properties remains challenging, as the widely used electrospinning processes have certain limitations, such as poor yield, use of high voltage, and difficulty in achieving in situ nanofiber deposition on various substrates. This review highlights the insights into fabrication strategies, applications, recent clinical trials, and patents of nanofibers for different skin disorders in detail. Additionally, it discusses case studies of its effective utilization in the treatment of various skin disorders for a better understanding for readers.

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Insight into the pivotal role of signaling pathways in psoriasis pathogenesis, potential therapeutic molecules and drug delivery approaches

Cited by 18 publications

References 65 publications

Comprehensive analysis of crucial m6A-related differentially expressed genes associated with psoriasis

Comprehensive analysis of crucial m6A-related differentially expressed genes associated with psoriasis

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

Evolving Trends in Nanofibers for Topical Delivery of Therapeutics in Skin Disorders

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