Aggregation mechanism of cystatin c in neuronal cell and its implication in neurodegeneration

Abstract

Background: CystatinC (CysC) is an endogenous cysteine protease inhibitor, and expressed in all nucleated cells. This protein is mainly localized in lysosome, but is also secreted in body fluids. L68Q mutation of CysC increases its amyloid aggregation property, leading to Hereditary CysC Cerebral Amyloid Angiopathy. Moreover, CysC is known as a major component of Bunina bodies, an ALS-specific neuronal inclusion body, suggesting its relationship with neurodegeneration.