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NPC1L1

Nowadays, NPC1L1 is a topic on everyone's lips. From its impact on society to its influence on the economy, NPC1L1 has become a crucial point of discussion in various spheres. With a growing interest in this topic, it is important to delve into its different aspects and understand its relevance today. In this article, we will thoroughly explore NPC1L1 and analyze its role in different contexts. From its origin to its possible consequences, we will delve into the importance of understanding NPC1L1 in the current landscape. Join us on this tour of NPC1L1 and discover its impact on our society!

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NPC1L1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNPC1L1, NPC11L1, NPC1 like intracellular cholesterol transporter 1, SLC65A2, LDLCQ7
External IDsOMIM: 608010; MGI: 2685089; HomoloGene: 56585; GeneCards: NPC1L1; OMA:NPC1L1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

29881

237636

Ensembl

ENSG00000015520

ENSMUSG00000020447

UniProt

Q9UHC9

Q6T3U4

RefSeq (mRNA)

NM_001101648
NM_001300967
NM_013389

NM_207242

RefSeq (protein)

NP_001095118
NP_001287896
NP_037521

n/a

Location (UCSC)Chr 7: 44.51 – 44.54 MbChr 11: 6.16 – 6.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract's epithelial cells[5] as well as in hepatocytes.[6] Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of 15-20%.[7] Polymorphic variations in the NPC1L1 gene could be associated with non-response to ezetimibe treatment.[8] One study found that people with inactivating mutations in the NPC1L1 gene had a lower LDL cholesterol level, as well as an around 50% reduction in the risk of coronary heart disease.[9]

NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.[10]

As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial,[11] it had been hypothesized that NPC1L1 inhibition by ezetimibe might be associated with an increased cancer risk.[12] However, a meta-analysis of ezetimibe clinical data showed no increase in the risk of cancer from treatment with ezetimibe.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000015520 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020447 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8132–7. Bibcode:2005PNAS..102.8132G. doi:10.1073/pnas.0500269102. PMC 1149415. PMID 15928087.
  6. ^ Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe". The Journal of Clinical Investigation. 117 (7): 1968–78. doi:10.1172/JCI30060. PMC 1888567. PMID 17571164.
  7. ^ Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia". Journal of Atherosclerosis and Thrombosis. 14 (3): 99–108. doi:10.5551/jat.14.99. PMID 17587760.
  8. ^ Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt.
  9. ^ Myocardial Infarction Genetics Consortium Investigators; Stitziel, Nathan O.; Won, Hong-Hee; Morrison, Alanna C.; Peloso, Gina M.; Do, Ron; Lange, Leslie A.; Fontanillas, Pierre; Gupta, Namrata; Duga, Stefano; Goel, Anuj; Farrall, Martin; Saleheen, Danish; Ferrario, Paola; König, Inke (2014-11-27). "Inactivating mutations in NPC1L1 and protection from coronary heart disease". The New England Journal of Medicine. 371 (22): 2072–2082. doi:10.1056/NEJMoa1405386. ISSN 1533-4406. PMC 4335708. PMID 25390462.
  10. ^ Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine. 18 (2): 281–5. doi:10.1038/nm.2581. PMC 3530957. PMID 22231557.
  11. ^ Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". The New England Journal of Medicine. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.
  12. ^ Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials". The New England Journal of Medicine. 359 (13): 1357–66. doi:10.1056/NEJMsa0806603. PMID 18765432.
  13. ^ Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology. 201: 247–52. doi:10.1016/j.ijcard.2015.08.103. PMID 26301648.
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