Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,915 bioRxiv papers from 266,490 authors.

Histone deacetylase inhibitors correct the cholesterol storage defect in most NPC1 mutant cells

By Nina H. Pipalia, Kanagaraj Subramanian, Shu Mao, William E Balch, Frederick R. Maxfield

Posted 21 Sep 2016
bioRxiv DOI: 10.1101/076695 (published DOI: 10.1194/jlr.M072140)

Niemann Pick C disease (NPC) is an autosomal recessive disorder that leads to excessive storage of cholesterol and other lipids in late endosomes and lysosomes. The large majority of NPC disease is caused by mutations in NPC1, a large polytopic membrane protein that functions in late endosomes. There are many disease-associated mutations in NPC1, and most patients are compound heterozygotes. The most common mutation NPC1I1061T has been shown to cause endoplasmic reticulum associated degradation of the NPC1 protein. Treatment of patient derived NPC1I1061T fibroblasts with histone deacetylase inhibitors (HDACi) Vorinostat or Panobinostat increases expression of the mutant NPC1 protein and leads to correction of the cholesterol storage. Herein we show that several other human NPC1 mutant fibroblast cell lines can also be corrected by Vorinostat or Panobinostat and that treatment with Vorinostat extends the lifetime of the NPC1I1061T protein. To test effects of HDACi on a large number of NPC1 mutants, we engineered a U2OS cell line to suppress NPC1 expression by shRNA and then transiently transfected these cells with 81 different NPC1 mutant constructs. The mutant NPC1 did not significantly reduce cholesterol accumulation, but approximately 80% of the mutants showed reduced cholesterol accumulation when treated with Vorinostat or Panobinostat.

Download data

  • Downloaded 577 times
  • Download rankings, all-time:
    • Site-wide: 14,717 out of 57,915
    • In cell biology: 566 out of 2,749
  • Year to date:
    • Site-wide: 46,064 out of 57,915
  • Since beginning of last month:
    • Site-wide: 41,702 out of 57,915

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News