A1M, an extravascular tissue cleaning and housekeeping protein: a possible drug candidate

Alpha-1-microglobulin (A1M) is a small protein found intra- and extracellularly in all tissues of vertebrates. The protein was discovered 40 years ago and its physiological role remained unknown for a long time. A series of recent publications have demonstrated that A1M is a vital part of tissue housekeeping. A strongly electronegative free thiol group forms the structural basis of heme-binding, reductase- and radical-trapping properties. A rapid flow of liver-produced A1M through blood and extravascular compartments ensures clearing of biological fluids from heme and free radicals and repair of oxidative lesions. After binding, both the radicals and A1M are electroneutral and therefore do not present any further oxidative stress to tissues. The biological cleaning cycle is completed by glomerular filtration, renal degradation and urinary excretion of A1M heavily modified by covalently linked radicals and heme-groups. Based on its role as a tissue housekeeping cleaning factor, A1M constitutes a potential therapeutic drug candidate in treatment or prophylaxis of diseases or conditions that are associated with pathological oxidative stress elements.