Sterol O-acyltransferase 1 (SOAT1) (SOAT1)

Sterol O-acyltransferase 1 (SOAT1), also known as ACAT1, is an integral membrane enzyme located in the endoplasmic reticulum that catalyzes the formation of cholesterol esters from free cholesterol and long-chain fatty acyl-CoA (UniProt: P35610). This reaction is a critical component of intracellular cholesterol homeostasis, as it allows for the storage of excess cholesterol in cytoplasmic lipid droplets, thereby preventing the toxic accumulation of free sterols in cellular membranes (NCBI Gene: 6646). SOAT1 mRNA has become a target of therapeutic interest because its protein product is significantly upregulated in several aggressive cancers, including pancreatic cancer, glioblastoma, and hepatocellular carcinoma, where it supports rapid tumor growth and metastasis by modulating lipid signaling and membrane synthesis (Geng et al., 2016, Nat Commun). In neurobiology, SOAT1 is a key player in Alzheimer's disease pathogenesis; its inhibition has been shown to reduce the production of amyloid-beta peptides and promote the clearance of existing plaques in preclinical models (Puglielli et al., 2001, Nat Cell Biol). While small-molecule inhibitors like avasimibe were originally developed for atherosclerosis, current research is exploring the use of antisense oligonucleotides (ASOs) and siRNA to specifically knockdown SOAT1 mRNA to treat cancer and neurodegeneration. However, therapeutic strategies must carefully balance the reduction of cholesterol esters with the risk of inducing lipotoxicity from free cholesterol buildup, which can lead to cell death if not properly managed (PubMed: 27018613).

Other names

ACAT1Acyl-CoA:cholesterol acyltransferase 1Cholesterol acyltransferase 1ACACTASAT1

Antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) target the SOAT1 mRNA for degradation via RNase H-mediated cleavage or the RNA-induced silencing complex (RISC), respectively, thereby reducing the translation of the Sterol O-acyltransferase 1 enzyme and decreasing the esterification of intracellular cholesterol (PubMed: 27018613, 11590443).