Université de Toulose, Hôpital Purpan, Toulouse, France.
Eur J Dermatol. 2011 May;21 Suppl 2:35-42. doi: 10.1684/ejd.2011.1264.
Corneodesmosin (CDSN) was identified 20 years ago by raising monoclonal antibodies against human plantar stratum corneum. The protein is specific to corneodesmosomes, cell-junction structures that, in humans, are found in the epidermis, the hard palate epithelium, and the inner root sheath of the hair follicles. Synthesized by the granular keratinocytes and secreted via the lamellar bodies, CDSN is incorporated into the desmoglea of the desmosomes, shortly before their transformation into corneodesmosomes during cornification. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface prior to desquamation. The recent inactivation of Cdsn in mice induced a lethal epidermal barrier disruption and hair follicle degeneration, related to corneodesmosome dysfunction. That confirmed the essential role of the protein in maintaining integrity of the epidermis and the hair follicle. The CDSN gene is located in PSORS1, the major psoriasis susceptibility locus on the chromosome 6, but to date its involvement in the disease pathophysiology is not clear. By contrast, two different monogenic diseases associated with nonsense mutations in CDSN, were recently identified. First, hypotrichosis simplex of the scalp in which mutated CDSN accumulates in the dermis and forms amyloid deposits; then, peeling skin disease in which the genetic defect induces dyscohesion of the stratum corneum, responsible for abnormal desquamation and increased skin penetration of allergens.
角蛋白桥粒芯糖蛋白（CDSN）20 年前被鉴定出来，当时人们针对人足底角质层制备了单克隆抗体。该蛋白是桥粒芯胶的特异性蛋白，桥粒芯胶是细胞连接结构，在人类中存在于表皮、硬腭上皮和毛囊内根鞘。CDSN 由颗粒状角质形成细胞合成，并通过板层小体分泌，在角蛋白转化为桥粒芯胶之前被整合到桥粒的桥粒芯胶中。CDSN 具有黏附特性，主要归因于其 N 端富含甘氨酸的结构域，并且在角质形成细胞向皮肤表面迁移以进行脱屑之前，随着其序列被蛋白酶逐步水解，其结构被逐步破坏。最近在小鼠中敲除 Cdsn 会导致致命的表皮屏障破坏和毛囊退化，这与桥粒芯胶功能障碍有关。这证实了该蛋白在维持表皮和毛囊完整性方面的重要作用。CDSN 基因位于 PSORS1 上，PSORS1 是染色体 6 上主要的银屑病易感基因座，但迄今为止，其在疾病发病机制中的作用尚不清楚。相比之下，最近鉴定出两种与 CDSN 无义突变相关的不同单基因疾病。首先是头皮单纯性毛发稀少症，突变的 CDSN 在真皮中积累并形成淀粉样沉积物；然后是剥脱性皮肤病，遗传缺陷导致角质层不黏合，导致异常脱屑和过敏原更易穿透皮肤。
