Impaired cerebellar granule neuron proliferation in Niemann-Pick C1 mice is corrected by a single hydroxyproplyl-betacyclodextrin injection

Niemann Pick type C (NPC) disease is an autosomal recessive, neurodegenerative lysosomal storage disorder due to the abnormal function of NPC1 or NPC2 (95% and 5% of NPC patients, respectively) proteins, involved in intracellular trafficking of cholesterol and other lipids. The deficiency of either protein leads to the accumulation of endocytosed unesterified cholesterol and other lipids, including spingomielin and gangliosides within lysosomes. The classic presentation of NPC disease is a child of either sex developing coordination problems, dysarthria and hepatosplenomegaly during early school-age years. A prominent feature of NPC1 disease in humans is the massive loss of cerebellar Purkinje cells (PCs). A similar feature is also observed in several mouse models of NPC1 disease, in which PC degeneration and loss initiates at PN28-PN40 and becomes very pronounced at PN60. Despite the huge interest for mechanisms underlying PC degeneration, the effect of Npc1 loss of function on over