The Different Biologically Active Forms of Alpha-Fetoprotein as Functional Biomarkers in Pregnancy, Disease and Cancer: A Review and Update

Abstract

Human alpha-fetoprotein (HAFP) has been known to manifest in multiple structural forms as previously reported in the biomedical literature. Such structural forms of HAFP have included isoforms, epitopes, carbohydrate and pH heterogenetic forms, and structural variants. However, within the last decade, studies have reported variant forms of HAFP not necessarily of a structural nature as reported in the literature. These newer forms of HAFP are largely functional forms in contrast to structural variants. Such functional forms are a result of slightly denatured intermediates (molten globule forms), conformational variants, misfolded proteins, conformationally transformed HAFP molecules, non-secreted forms, and synthetic peptide segments/sequences derived from the HAFP polypeptide. These latter bioactive functional forms of HAFP have been discussed in the present report. Such recently described forms of the oncofetal protein are deemed of importance since they can be utilized as functional bioactive markers during pregnancy, perinatal, perineurium and juvenile stages, in addition to benign and/or malignant tumor growths in adults.