Friday, October 29, 2010

Filaggrin, I love ya

I wasn't going to post today-- a bit worn out after taking the kids to a Hallowe'en party and trying to keep Voov (wearing cute flower costume, for the second year) from eating soup and noodles, which are off-limits due to her food restrictions, while trying to keep Shmoop (wearing cute lion costume, for the third year) out of the desserts. Successful with the soup & noodles. Less successful with the dessert. And so, while Voov sits placidly in the bath, Shmoop has a giant screaming and kicking fit as he comes off his sugar high, and must be manhandled to bed.

But I just can't stop wanting to learn more about filaggrin. It's my protein of the month. Here's something else I found today: a 2009 review of the role of filaggrin in atopic dermatitis. (Several studies have positively linked two mutations in the filaggrin gene to a significantly higher risk of eczema.)

So: as I wrote last Saturday, filaggrin is this protein that skin cells start to produce as they move along the treadmill from the inner zones of the skin to the stratum corneum. When the skin cells get to the stratum corneum, filaggrin gets chopped up into short bits called peptides, and these peptides grab hold of the inner keratin skeleton of the cell and pull it all together, flattening the cells. A loss-of-function mutation in filaggrin means that your skin's outer layer is defective and, from the very first, it lets in many more pathogens and allergens than "normal" skin-- which may overstimulate the immune system and cause you to develop chronic allergies.

And now, in the 2009 review (which is a year old, so more has been learned since then) I find that filaggrin is no one-trick pony. It's more than a keratin scrunchie. Within the stratum corneum, the filaggrin peptides get progressively degraded and altered unto a mix of amino acids that, along with some ions, is called the "natural moisturizing factor." The natural moisturizing factor is, basically, your own Eucerin, and prevents water loss; it's also slightly acidic.

So when you have mutated filaggrin, not only does it mess up the structure of your skin cells, but it doesn't get processed into moisturizer, and your skin pH is too alkaline-- which has been reported to affect the composition of your T cell populations in the skin, and lead to inflammation.


In the last paragraph of these papers, the authors always say something like "this work could lead to targeted intervention and therapy." (They have to, to justify more funding.) At some point, we, the funders, must ask: where's the beef? Tell us how this research is going to lead to therapy. New drugs? How exactly will they be discovered? New emollient strategies? Who's formulating them? And is there going to be any relief for adults who are already well along the atopic march?

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