Insulin-degrading enzyme: embarking on amyloid destruction

Several human disorders are caused by or associated with the deposition of protein aggregates known as amyloid fibrils, Despite the lack of sequence homology among amyloidogenic proteins, all amyloid fibrils share a common morphology. are insoluble under physiological conditions and are resistant to proteolytic degradation. Because amyloidogenic proteins are being produced continuously, eukaryotic organisms must have developed a form of proteolytic machinery capable of controlling these aggregation-prone species before their fibrillization. This article suggests that an intracellular metalloprotease called insulin-degrading enzyme (IDE) is responsible for the elimination of proteins with amyloidogenic potential and proposes a mechanism for the selectivity of the enzyme. In this respect, IDE can also be referred to as ADE: amyloid-degrading enzyme.