Small Proline-Rich Protein (SPRR) Inhibitors

The Small Proline-Rich Protein (SPRR) family is a group of proteins characterized by their rich content in proline and are part of the epidermal differentiation complex. These proteins are primarily expressed in the skin, where they play a pivotal role in the formation of the cornified envelope, a structure critical for the barrier function of the skin. SPRR proteins are involved in the response to mechanical and environmental stress, aiding in skin repair and regeneration. Their expression is highly inducible and is often upregulated in response to skin injuries, inflammation, and certain pathological conditions like psoriasis. On a molecular level, SPRR proteins interact with other components of the cornified envelope, such as loricrin and filaggrin, to form a robust and resilient barrier. This barrier is essential not only for protecting against physical and chemical insults but also for excessive water loss.

Targeting Small Proline-Rich Proteins (SPRRs) for disruption or inhibition using small molecules offers a strategic approach to unravel the complex mechanisms of the skin's defense system. By selectively inhibiting SPRRs, researchers can observe the consequent effects on the skin's barrier function and antimicrobial activity, revealing the specific roles these proteins play in cutaneous defense. This approach allows for the detailed study of how SPRRs contribute to the structural integrity of the epidermal barrier and their direct action in antimicrobial defense, particularly their role in bacterial membrane disruption. Inhibiting SPRRs can also help in understanding their interaction with other components of the skin's defense system, such as other antimicrobial peptides, immune cells, and signaling molecules.