Brefeldin A (BFA)¹ is a macrocyclic lactone synthesized from palmitate (C₁₆) by a variety of fungi. It was initially isolated and characterized in the 1960s as an antiviral antibiotic.^2,3 In the late 1980s it was found to act as a very powerful inhibitor of intracellular protein transport.^4-6 BFA specifically and reversibly blocks protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus in many cell types and species.^7,8 These effects are generally accompanied by distinct structural changes expressed in apparent collapse of the Golgi stacks and its redistribution into the ER as well as into the nuclear envelope,^6,7 which leads to inhibition of protein secretion, vesicular assembly and antigen presentation.^3-9 A large body of evidence demonstrates that BFA inhibits the whole cell membrane traffic by its ability to inhibit binding of regulatory coat proteins to their target organelles. In this way, BFA deregulates membrane traffic throughout the central vacuolar system of the cell.⁸

BFA was also shown to act as a mitosis inhibitor in plant cells, and as a cancerostatic and apoptosis inducer in animal cells.^6-10

BFA is very effective for enhancing accumulation of intracellular cytokines and it has relatively low toxicity (LD₅₀ in mice (intraperitoneal injection) >200 mg/kg).¹⁰ Due to its peculiar activity, BFA is used as an inducer of pathogenesis in models of neurodegenerative diseases.^10-13