Keratin and other disulfide bond–containing structural proteins

Keratins are a diverse group of intermediate filament proteins that provide essential mechanical support and structural integrity to epithelial tissues, including the skin, hair, and nails (Bragulla & Homberger, 2009). These proteins are characterized by a high concentration of cysteine residues, which facilitate the formation of extensive inter-chain disulfide bonds, resulting in a tough, insoluble, and chemically resistant matrix (NCBI, 2023). In pharmacology, these disulfide-rich structures are targeted by reducing agents, such as thioglycolic acid, which break the S-S bonds to allow for the physical reshaping of hair (PubChem). Keratolytic agents like salicylic acid and urea are used to treat hyperkeratotic disorders by disrupting the cohesion between keratinocytes, thereby promoting the shedding of the stratum corneum (StatPearls, 2023). Additionally, the keratophilic nature of certain antifungal drugs, such as terbinafine and griseofulvin, allows them to accumulate in keratinized tissues, making them effective against dermatophyte infections (Gupta et al., 2012). Mutations in specific keratin genes are associated with various genetic diseases, such as epidermolysis bullosa simplex, where the loss of structural support leads to severe tissue fragility (UniProt).

Other names

CytokeratinIntermediate filament proteinsS-S bonded structural proteinsCornified envelope proteins

Reduction of disulfide bonds (cleaving S-S to -SH), disruption of non-covalent protein-protein interactions (keratolysis), and high-affinity sequestration/binding by keratophilic agents.