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NPC1, intracellular cholesterol trafficking and atherosclerosis
Xiao-Hua Yu1, Na Jiang2, Ping-Bo Yao3
1Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
Clinica Chimica Acta; International Journal of Clinical Chemistry
|December 4, 2013
Summary
Niemann-Pick type C1 (NPC1) protein regulates cholesterol transport from late endosomes/lysosomes. Defects in NPC1 cause Niemann-Pick disease and contribute to atherosclerosis progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Cardiovascular Disease Research
Background:
- Intracellular cholesterol trafficking is crucial for lipid homeostasis.
- Niemann-Pick type C1 (NPC1) protein facilitates cholesterol transport from late endosomes/lysosomes (LE/LY) to the endoplasmic reticulum (ER) and plasma membrane.
- Mutations in NPC1 cause Niemann-Pick disease, characterized by lipid accumulation in LE/LY.
Purpose of the Study:
- To review the role of NPC1 in intracellular cholesterol trafficking.
- To summarize NPC1's involvement in the progression of atherosclerosis.
Main Methods:
- Literature review of studies on NPC1 function.
- Analysis of NPC1's role in lipid homeostasis and disease pathology.
Main Results:
- NPC1, with NPC2 and OSBP-related protein 5 (ORP5), mediates cholesterol transport.
- Liver X receptor (LXR) positively regulates NPC1 expression.
- NPC1 plays a critical role in atherosclerotic progression.
Conclusions:
- NPC1 is a key regulator of post-lysosomal cholesterol trafficking.
- Understanding NPC1's function is vital for addressing Niemann-Pick disease and atherosclerosis.
Keywords:
ABCA1ATP-binding cassette transporter A1AtherosclerosisCOX-2CholesterolDHCERERK1/2LDLLDL-CLDL-cholesterolLDLRLE/LYLXRN-terminal domainNPC1NPC2NTDNiemann-Pick type C1ORP5OSBPOSBPrelated protein 5PPARαSREBPSSDTGNapoA-IapoEapolipoprotein A-Iapolipoprotein Ecyclooxygenase-2dihydrocapsaicinendoplasmic reticulumextracellular signal-regulated kinase 1/2late endosome/lysosomeliver X receptorlow-density lipoproteinlow-density lipoprotein receptoroxLDLoxidized low-density lipoproteinoxysterolbinding proteinperoxisome proliferator-activated receptor αsterol regulatory element-binding proteinsterol-sensing domaintrans-Golgi network
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