Signaling Proteins as Targets for Atopic Eczema
Atopic eczema, the most common type of eczema, significantly impacts quality of life. Its complexity, influenced by genetic, environmental, and immunological factors, underscores the importance of target discovery for innovative treatments. Identifying novel targets may pave the way for more effective treatments that address the underlying causes of disease.
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Overview
Atopic eczema, the most common type of eczema, significantly impacts quality of life. Its complexity, influenced by genetic, environmental, and immunological factors, underscores the importance of target discovery for innovative treatments.
An Introduction to Atopic Eczema
Atopic eczema, also know as atopic dermatitis, is a prevalent inflammatory skin disease affecting up to 25% of children.¹ This disease is characterized by skin barrier abnormalities and immunological dysregulation.² Clinical manifestations include dry skin, itchiness and red rashes. Atopic eczema not only causes physical discomfort, but also emotional distress, culminating in reduced quality of life.
Current treatments for atopic eczema include topical corticosteroids, moisturizers and calcineurin inhibitors, all designed to mitigate symptoms. Recently monoclonal antibodies have emerged as a promising treatment option for atopic eczema. Among these, dupilumab and tralokinumab have shown to be found to be effective against eczema.³ Despite existing treatments, there is a vital need for targeted therapies to address the diverse manifestations and underlying causes of atopic eczema.
Target Identification and Prioritization
Using Causaly, approximately 1500 targets for atopic eczema were instantly uncovered and presented as a dendrogram view of results. While there are no direct medications targeting the FLG gene – which is mutated in atopic eczema⁴ – it remains one of the most studied targets for this disease.
Targets can be further prioritized into those reported in primary data of in vivo studies, more than half of which have been reported in the literature in the last 5 years. Owing to their role in inflammatory pathways and immune responses, targets were further refined by target subclass, revealing around 90 signaling proteins as potential targets for this disease.
Chemokine C-C motif ligand 2 (CCL2) and mesencephalic astrocyte-derived neurotrophic factor (MANF) were identified as signaling protein targets with strong effects on atopic eczema, despite the number of studies being limited.
- CCL2, also known as MCP-1, is a chemokine that recruits monocytes to sites of inflammation. Elevated expression of CCL2 has been implicated in various skin conditions, highlighting its role in the pathogenesis of dermatological conditions. CCL2 has been reported as a survival factor and pathogenic inducer of atopic eczema.⁵ More recently, Poncirus trifoliata (L.) Raf. was found to suppress the secretion of MCP-1 and other inflammatory cytokines in HaCaT cells, as well as alleviate atopic dermatitis-like symptoms in mice.⁶
- MANF: Primarily recognized for its neuroprotective properties and stress response, MANF can influence inflammation and tissue repair. Recent studies have illuminated its significance in skin diseases. A study demonstrated that cold atmospheric plasma treatment upregulates the expression of MANF, which in turn alleviates skin inflammation and other atopic eczema symptoms in a mouse model.⁷
Conclusion
The multifaceted nature of atopic eczema demands innovative therapeutic approaches. Here, we explored the potential of signaling proteins as targets for this disease due to their roles in inflammation and skin repair. Identifying novel targets may pave the way for more effective treatments that address the underlying causes of disease.
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