Copper-induced cytotoxicity: reactive oxygen species or islet amyloid polypeptide oligomer formation

摘要

Copper enhances amyloid cytotoxicity and mediates human islet amyloid polypeptide (hIAPP) oligomerization; nickel, a redox inactive metal with similar protein binding affinity to copper, also mimics this effect, thereby demonstrating copper-mediated hIAPP cytotoxicity is due mainly to granular oligomer generation rather than ROS accumulation in type 2 diabetes.rnMany human disorders are characterized by amyloid accumulation, notably Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), and Parkinson's disease. These diseases share common pathological features: smaller prefibrillar oligomers are cytotoxic for living systems rather than mature amyloid fibrils proposed previously.