There is a compelling body of evidence indicating an association between cholesterol and Alzheimer's disease (AD). Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), an endoplasmic-reticulum-resident enzyme that catalyses the formation of cholesteryl esters (CEs) from cholesterol and long-chain fatty acids, modulates the generation of beta amyloid peptide (Abeta). A single nucleotide polymorphism rs1044925 in the sterol O-acyltransferase 1 (SOAT1), the gene encoding ACAT1, has been reported to be association with an increased risk for sporadic AD (SAD) in European population. In the present study, we examined the association of the SOAT1 rs1044925 polymorphism with SAD in our northern Han-Chinese (107 cases, 118 age and gender-matched controls) sample using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There was no genotypic (chi(2)=0.030, OR 0.942, 95% CI=0.478-1.857) or allelic (chi(2)=0.021, OR 0.955, 95% CI=0.508-1.794) association between SAD and controls, even when the data were stratified by APOEvarepsilon4 carrier status. Our results indicate that the polymorphism rs1044925 in the 3'UTR of SOAT1 gene does not affect the risk of SAD in the northern Han-Chinese.
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http://dx.doi.org/10.1016/j.neulet.2005.06.020 | DOI Listing |
Nutrients
January 2025
Department of Food & Nutrition, Kyung Hee University, Seoul 02447, Republic of Korea.
Background/objectives: The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and Se in ameliorating MASH induced by a methionine choline-deficient (MCD) diet in mice.
View Article and Find Full Text PDFCell Rep
January 2025
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address:
Sterols target sterol-sensing domain (SSD) proteins to lower cholesterol and circulating and hepatic triglyceride levels, but the mechanism remains unclear. In this study, we identify acyl-coenzyme A (CoA) synthetase long-chain family member 1 (ACSL1) as a direct target of ergosterol (ES). The C-terminal domain of ACSL1 undergoes conformational changes from closed to open, and ES may target the drug-binding pocket in the acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1 to stabilize the closed conformation and maintain its activity.
View Article and Find Full Text PDFPhysiol Rev
April 2025
Institute of Metabolism and Cell Death, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany.
We present here a comprehensive update on recent advancements in the field of ferroptosis, with a particular emphasis on its metabolic underpinnings and physiological impacts. After briefly introducing landmark studies that have helped to shape the concept of ferroptosis as a distinct form of cell death, we critically evaluate the key metabolic determinants involved in its regulation. These include the metabolism of essential trace elements such as selenium and iron; amino acids such as cyst(e)ine, methionine, glutamine/glutamate, and tryptophan; and carbohydrates, covering glycolysis, the citric acid cycle, the electron transport chain, and the pentose phosphate pathway.
View Article and Find Full Text PDFResearch (Wash D C)
November 2024
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 Zhejiang, China.
Clear cell renal cell carcinoma (ccRCC) is a prevalent malignant tumor of the urinary system. While tyrosine kinase inhibitors (TKIs) are currently the first-line treatments for advanced/metastatic ccRCC, patients often develop resistance after TKI therapy. Lipid metabolic reprogramming, a hallmark of tumor progression, contributes to acquired drug resistance in various malignant tumors.
View Article and Find Full Text PDFPharmaceutics
October 2024
Centro di Ricerca Coordinata sulle Interazioni Farmacologiche, 20122 Milan, Italy.
Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug-drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg.
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