Protein misfolding and toxicity in dialysis-related amyloidosis

Abstract

Amyloid formation from the protein precursor β2-microglobulin (β2m) is implicated in the human pathology dialysis-related amyloidosis (DRA). The first report of the clinical symptoms of the pathology was noted in 1975, but the amyloid basis for the pathology was not realized until 1980, and the precursor protein was identified as β2m in 1985 (Warren and Otieno, Postgrad Med J 51:450-452, 1975; Assenat et al., Nouv Presse Med 9:1715, 1980; Gejyo et al., Biochem Biophys Res Commun 129:701-706, 1985). Here we discuss the physiological role of β2m as a component of the major histocompatibility complex class I (MHC I); the clinical implications of DRA; the current knowledge of β2m aggregation resulting from in vitro models; and how this has informed our understanding of the molecular basis of the disease. In particular, the role of toxic oligomers in the pathology of DRA is considered.