Niemann-Pick type C1 disease
This neurodegenerative lysosomal storage disorder is caused by mutations in the acidic compartment protein NPC1. The function of NPC1 is unknown, but when it is dysfunctional, sphingosine, glycosphingolipids, sphingomyelin and cholesterol accumulate in the lysosome and eventually leads to disease.
This build up of lipids is thought to be a result of a reduced calcium influx into the lysosome disrupting normal lysosomal function. I am involved in research trying to understand the molecular basis of how defective NPC1 protein causes altered calcium homeostasis and why this eventually causes disease.
Key Points:
- Abnormal accumulation of lipids in lysosomes in NPC1 patients.
- Evidence that the primary defect is due to abnormal lysosomal calcium influx.
- Identify the molecular basis of how NPC1 mutations lead to abnormal calcium homeostasis and disease.
This work is supported by Target ALS
