Filaggrin: the key to understanding and managing atopic dermatitis

Background: Atopic dermatitis is a chronic inflammatory genetically determined skin disease with high prevalence, significant negative impact on the quality of life of patients. Disruption of the skin barrier in AtD is closely associated with a deficiency of filaggrin, a key structural protein of the epidermis. Mutations of the FLG gene leading to loss of protein function are the most important genetic risk factor for AtD, significantly aggravating its course and prognosis. Currently, active research is underway to develop effective methods to restore filaggrin deficiency, which represents a promising direction of therapy of atopic dermatitis.

Matherials and Methods: A systematic literature analysis in PubMed, Google Scholar, ClinicalTrials.Gov databases was performed to search for modern approaches to restore the skin barrier in atopic dermatitis by affecting filaggrin and its metabolism.

Results: Promising strategies to target filaggrin were highlighted: direct replacement therapy using recombinant forms of FLG, use of metabolites (L-histidine, cis-urocanic acid), plant extracts, and mechanical stimulation methods. The presented approaches demonstrate the ability to improve skin barrier functions and attenuate inflammatory processes, but need to confirm clinical efficacy and clarify the mechanisms of action.

Conclusion: Current strategies for correction of filaggrin deficiency have high potential for AD therapy, but require further research, including at the molecular and clinical levels, in order to be implemented in clinical practice.