NPC1 disease is characterized by neurodegeneration caused by cholesterol accumulation. In this study, defective internalization of GluR2-containing AMPA receptors in NPC1-/- neurons is found to be related to dysfunctional mGluR1/5. Stimulation of mGluR1/5 increases the internalization and downregulates over-influx of calcium. Moreover, p-GluR2 and PKC are proposed to be involved in this regulation. Our data imply that abnormal internalization of AMPA receptors is a critical mechanism for neuronal dysfunction and correction of mGluR1/5 is a potential therapeutic strategy for NPC1 disease.<eng>
