Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease - PubMed
12 hours ago
- #cholesterol accumulation
- #Rab7-GTPase
- #Niemann-Pick type C
- Small molecules identified to elevate Rab7-GTPase activity can reduce cholesterol accumulation in Niemann-Pick type C (NPC) disease.
- The study focused on pharmacologically interfering with TBC1D15-mediated Rab7 inactivation to upregulate Rab7 activity.
- Four drug candidates were found effective in reducing cholesterol accumulation in various NPC1 mutant models, including CHO M12 cells, NPC1 patient fibroblasts, and neuronal cells.
- The drug candidates also enhanced the cholesterol removal effect of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in treated cells.
- The identified small molecules did not negatively impact cell viability or cause membrane damage.
- Elevating Rab7-GTPase activity offers potential therapeutic opportunities for NPC disease and other Rab7-related neurological disorders.