Neurodevelopment

PATHOGENETIC MECHANISMS RESPONSIBLE FOR ALTERED DEVELOPMENTAL TRAJECTORIES IN NIEMANN PICK C DISEASE

Niemann Pick type C (NPC) disease is an autosomal recessive, neurodegenerative
lysosomal storage disorder caused by the abnormal function of NPC1 or NPC2 (95%
and 5% of NPC patients, respectively), proteins involved in the intracellular
trafficking of endocytosed cholesterol and other lipids.
The accumulation/mislocalization of cholesterol, gangliosides, sphingolipids alters
signaling pathways, likely causing developmental defects. As an example, the
covalent cholesterol modification of Sonic hedgehog (Shh) and its downstream

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