Filaggrin and the great epidermal barrier grief.
One of the principal functions of human skin is to form an effective mechanical barrier against the external environment. This involves the maturation and death of epidermal keratinocytes as well as the assembly of a complex network of differentially and spatially expressed proteins, glycoproteins and lipids into the keratinocyte cell membrane and surrounding extracellular space. In 2006, the key role of the granular cell layer protein filaggrin (filament-aggregating protein) in maintaining the skin barrier was determined with the identification of loss-of-function mutations in the profilaggrin gene (FLG). These mutations have been shown to be the cause of ichthyosis vulgaris and a major risk factor for the development of atopic dermatitis, asthma associated with atopic dermatitis as well as systemic allergies. Mutations in the FLG gene are extremely common, occurring in approximately 9% of individuals from European populations. The remarkable discovery of these widespread mutations is expected to have a major impact on the classification and management of many patients with ichthyosis and atopic disease. It is also hoped that the genetic discovery of FLG mutations will lead to the future development of more specific, non-immunosuppressive treatments capable of restoring effective skin barrier function and alleviating or preventing disease in susceptible individuals.
McGrath
John A
JA
Genetic Skin Disease Group, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, The Guy's, King's College and St Thomas' School of Medicine, London, UK. john.mcgrath@kcl.ac.uk
D002454:Cell Differentiation / Q000502:physiology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000503:physiopathology; D004817:Epidermis / Q000503:physiopathology*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000503:physiopathology; D016112:Ichthyosis Vulgaris / Q000235:genetics* / Q000503:physiopathology; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology*; D009154:Mutation; D012871:Skin Diseases / Q000235:genetics / Q000503:physiopathology
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins