Pregnancy zone protein (PZP)

Pregnancy zone protein (PZP) is a large, secreted plasma glycoprotein that belongs to the alpha-2-macroglobulin family and is highly upregulated during pregnancy. Structurally, it functions as a homotetramer or homodimer and inhibits all four classes of proteinases via a unique 'trapping' mechanism involving a bait region; cleavage here induces a conformational change that traps and covalently binds the proteinase. PZP is also recognized for potent extracellular chaperone activity, sequestering amyloid beta and other misfolded proteins to limit fibril formation. In pregnancy, PZP plays a central immunomodulatory role by dampening maternal Th1 immune responses and may function in concert with placental proteins such as Glycodelin A. Its hepatic synthesis is highly responsive to estrogens, making it the most estrogen-sensitive hepatic protein described. PZP levels are also elevated in the sera of presymptomatic Alzheimer’s patients and are upregulated in cellular senescence, implicating broader roles in neurodegeneration and aging. There are no known drugs targeting PZP nor evidence of safety issues as it is not a current therapeutic target.

Other names

CPAMD6C3 and PZP-like alpha-2-macroglobulin domain-containing protein 6pregnancy-zone proteinpregnancy-associated α2-glycoproteinalpha-2-macroglobulin likeα2-pregnoglobulinXh-antigenSchwangerschaftsprotein-3Pα-1pregnancy-associated α-macroglobulinpregnancy-associated globulinα2-PAG