Filaggrin: Definition Of This Protein
Filaggrins are filaments associated proteins which bind to keratin fibres in epidermal cells. It is derived from keratohyalin granules, as are other keratinaceous proteins. These are essential protein in the horny layer of the skin. It plays key role of impaired skin barrier function in the development of atopic diseases.
Filaggrin: How it is formed.
The keratinocytes in stratum granulosum are characterized by keratohyalin granules containing abundant quantities of profilaggrin and loricrin proteins. The precursor of filaggrin is profilaggrin,which contains many filaggrin chains joined by tyrosine rich linker regions,it is highly phosphorylated on the serine residue. Each repeating unit of profilaggrin is processed to filaggrin, all phosphates are removed and the linker regions cleaved. After the keratin is aggregated by filaggrin, the arginine of filaggrin is converted to the uncharged citrulline, thereby dissociating it from the keratin. Then it is digested by proteolytic enzyme to the natural moisturizing factor.
Filaggrin: Important functions
Filaggrin is key protein that facilitates the terminal differentiation of the epidermis and formation of the skin barrier. It’s a protective barrier that keeps moisture in and infectious organisms out.
Filaggrin helps aggregate or stack the keratin fibres and is ultimately degraded in the upper layers to form amino acids, pyrrolidone, carboxylic acid and lactic acid in the startum corneum. These products are thought to function as natural moisturizing factor.
Filaggrin:Diseases Due To Deficiency Or Mutation
Individuals with truncation mutation in the gene coding for filaggrin are strongly predisposed to a severe form of dry skin ichthyosis vulgaris. About 1 in 500 people carry two defective copies of the gene. These people make no filaggrin and so suffer from this severe persistent disease, ichthyosis vulgaris.
It has beens shown that almost 50% of all severe cases of eczema may have atleast one mutated filaggrin gene.
The barrier defect seen in filaggrin null carriers also appears to lead to increased asthama susceptibility and exacerbations because the defective barrier may well allow continual presentation of antigens and allergens to the immune system via the skin . This lead to asthma in some cases. Asthma result may be surprising since filaggrin is not present in the respiratory tract but appears to be of importance in the skin only . A weakened skin barrier function might enable allergens to penetrate more easily and thereby promote the development of allergies. So lack of filaggrin plays a decisive role in the origins of allergies.
Variation in filaggrin gene which raise to develop atopic dermatitis more than threefold. In addition these genetic variations predispose to hay fever in those with atopic dermatitis.
About 10% of the population carry a single defective copy and have dry and flaky skin. Impairment of skin barrier function leads to epidermal water loss and leading to dry skin condition. Even cases of allergies such as reaction to nickel which is often found in costume jewelery.
Steps To Be Taken Along This Pathway:
Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated . while gene targeted therapy may not be available anytime soon. The next thing to do is to examine the metabolic pathway of this important protein in addition, to clarify which molecular mechanisms play a role at the genetic level but also concerning the protein itself then final aim ofcourse is to find out a therapy patient with atopic diseases.
And the last thing to say is if lack of filaggrin is such an important factor in allergic diseases, it would be almost conceivable to increase the production of this protein.