http://precedings.nature.com/tags/Cholesterol Recently posted documents tagged with 'Cholesterol' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/2163/version/1 Disorders of cholesterol biosynthesis have clinical manifestations involving skeleton, eyes, neurologic development, and skin. We describe a patient with congenital cataracts, developmental delay, microcephaly, and low serum cholesterol who developed severe psoriasiform dermatitis and arthralgias beginning at age 3. Her brain MRI indicatedminor gliosis. Quantitative sterol analysis of patient plasma and skin showed marked elevation of 4alpha-methyl- and 4, 4’-dimethylsterols, indicating a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Molecular studies showed mutations in SC4MOL, a gene predicted to encode a sterol C4 methyl oxidase. Thus, our patient has a previously undescribed inborn error of cholesterol biosynthesis. Cellular studies with patient-derived fibroblasts showed higher mitotic rate than control cells in cholesterol-depleted medium, in which de novo cholesterol biosynthesis was increased with the accumulation of methylsterol. Immunologic analyses showed dysregulation of immune-related receptors in the patient and her father. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts or in fresh leukocytes induced activation of cell cycle, and immune receptor dysregulation. These findings suggest that methylsterols influence mitotic capacity and immune function. SC4MOL is situated within the psoriasis susceptibility locus PSORS9, and is likely a genetic risk factor for common psoriasis. http://precedings.nature.com/documents/2163/version/1 Thu, 07 Aug 2008 12:47:36 UTC Mutations in the SC4MOL gene encoding a novel methyl sterol oxidase cause autosomal recessive psoriasisiform dermatitis, microcephaly and developmental delay hdl:10101/npre.2008.2163.1 2008-08-07 Miao He Nature Precedings 2008-08-07T12:47:36Z Manuscript Genetics & Genomics Immunology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1246/version/1 Background. Previous epidemiological and experimental studies indicated cholesterol as a central player in Alzheimer disease (AD). Here, we utilized skin fibroblasts and PBMC as possible ex vivo models for the study of dysfunctions of cholesterol homeostasis which may be related to AD development. Methods. We analyzed cholesterol homeostasis using colorimetric, thin layer chromatography (TLC), and histologic technique in ex vivo cultures of skin fibroblasts and PBMCs from patients with probable AD and their first-degree relatives. Additionally, healthy age-matched individuals served as controls. Findings. As compared to controls, skin fibroblasts and PBMCs from AD patients, displayed an evident alteration of cholesterol metabolism; namely an anomalous accumulation of cholesterol esters in their cytoplasm. No change in intracellular free cholesterol was observed. Cellular overloading of cholesterol esters was dramatically increased after specific growth stimulation of the different cell types. Cholesterol ester accumulation was negatively correlated to plasma levels of high density lipoprotein cholesterol (HDL-C) and positively correlated with severity of cognitive symptoms measured by Mini-Mental State Examination (MMSE). Inhibitors of cholesterol esterification, such as progesterone and SaH, as well as a potent inhibitor of cell proliferation, RAD, were able to prevent accumulation of cholesterol esters. Interpretation. Changes of cholesterol esters in the peripheral compartment may be indicative of a systemic alteration of intracellular cholesterol homeostasis, which in turn might create a cellular milieu favourable to the production of ß-amyloid in the brain. Pathways that control cholesterol esterification might represent promising targets for novel diagnostic and therapeutic AD approaches. http://precedings.nature.com/documents/1246/version/1 Thu, 08 Nov 2007 10:41:33 UTC Changes in Cholesterol Metabolism in Peripheral Cells of Alzheimer Disease Patients and Their Relatives hdl:10101/npre.2007.1246.1 2007-11-08 Alessandra Pani Nature Precedings 2007-11-08T10:41:33Z Manuscript Molecular Cell Biology Neuroscience http://creativecommons.org/licenses/by/2.5/