Autophagy and Its Therapy in Lysosomal Storage Diseases

摘要

Niemann-Pick disease type C (NPC) is a progressive disorder characterized by cerebellar ataxia, cognitive impairment, seizures, vertical supranuclear gaze palsy, dysphagia, hearing loss, hepatic disease, and death typically by 20 years of age.1-2 Over350 disease-causing mutations have been identified in either the NPC1 or NPC2 gene.3 NPC1 and NPC2 proteins are critical for the movement of unesterified cholesterol and glycosphingolipids from the endosomal/lysosomal compartment to the Golgi apparatus, plasma membrane, and endoplasmic reticulum.4-5 Brain histology includes widespread neuronal cytoplasmic vacuolization, neuronal loss most severely affecting the Purkinje cells, and axonal spheroid formation.