Skin barrier dysfunction and filaggrin

Yeonjoon Kim, Kyung Min Lim

Research output: Contribution to journalReview articlepeer-review

53 Scopus citations

Abstract

Skin barrier dysfunction caused by endogenous or exogenous factors can lead to various disorders such as xerosis cutis, ichthyoses, and atopic dermatitis. Filaggrin is a pivotal structural protein of the stratum corneum (SC) and provides natural moisturizing factors that play a role in skin barrier functions. Filaggrin aggregates keratin filaments, resulting in the formation of a keratin network, which binds cornified envelopes and collapse keratinocytes to flattened corneocytes. This complex network contributes to the physical strength of the skin. Filaggrin is degraded by caspase-14, calpain 1, and bleomycin hydrolases into amino acids and amino acid metabolites such as trans-urocanic acid and pyrrolidone carboxylic acid, which are pivotal natural moisturizing factors in the SC. Accordingly, filaggrin is important for the pathophysiology of skin barrier disorders, and its deficiency or dysfunction leads to a variety of skin disorders. Here, the roles and biology of filaggrin, related skin diseases, and a therapeutic strategy targeting filaggrin are reviewed. In addition, several drug candidates of different mode of actions targeting filaggrin, along with their clinical efficacy, are discussed.

Original languageEnglish
Pages (from-to)36-48
Number of pages13
JournalArchives of Pharmacal Research
Volume44
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (2018R1D1A1B07042919) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HP20C0061).

Publisher Copyright:
© 2021, The Pharmaceutical Society of Korea.

Keywords

  • Atopic dermatitis
  • Filaggrin
  • Skin barrier
  • Skin disorders

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