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Open AccessJournal ArticleDOI

Central nervous system: cholesterol turnover, brain development and neurodegeneration

John M. Dietschy
- 01 Apr 2009 - 
- Vol. 390, Iss: 4, pp 287-293
TLDR
High rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development in the mouse and human, respectively.
Abstract
The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plasma, even in the newborn. However, high rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development. Once a stable brain size is achieved in the adult, cholesterol synthesis continues, albeit at a much lower rate, and this synthesis is just balanced by the excretion of an equal amount of sterol, either as 24(S)-hydroxycholesterol or, presumably, as cholesterol itself.

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Citations
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Malformation syndromes caused by disorders of cholesterol synthesis

TL;DR: In this paper, the authors reviewed clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis and HEM dysplasia.
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Cholesterol metabolism in neurons and astrocytes

TL;DR: An understanding of cholesterol metabolism in the brain and its role in disease requires a close look at individual cell types, including neurons and astrocytes, which are identified as net producers and consumers of cholesterol.
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Liver X receptors in lipid signalling and membrane homeostasis.

TL;DR: The role of LXRs in cholesterol and lipid metabolism and the emerging strategies to target the LXR pathway to treat metabolic diseases are discussed.

Thematic Review Series: Genetics of Human Lipid Diseases Malformation syndromes caused by disorders of cholesterol synthesis

TL;DR: Clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis), HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidyspl Asia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome are reviewed.
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The Role of Cholesterol in the Pathogenesis of NASH

TL;DR: This review examines the effects of excess FC in hepatocytes, Kupffer cells (KCs), and hepatic stellate cells (HSCs), and the subcellular mechanisms by which excess FC can induce cellular toxicity or proinflammatory and profibrotic effects in these cells.
References
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Journal ArticleDOI

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

TL;DR: The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review.
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Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor

TL;DR: It is shown that the class B scavenger receptor SR-BI is an HDL receptor, which mediates selective cholesterol uptake by a mechanism distinct from the classic LDL receptor pathway.
Journal ArticleDOI

Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.

TL;DR: It is shown that Niemann-Pick C1Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol, and resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.
Journal ArticleDOI

CNS synaptogenesis promoted by glia-derived cholesterol

TL;DR: Cholesterol complexed to apolipoprotein E-containing lipoproteins may explain the delayed onset of CNS synaptogenesis after glia differentiation and neurobehavioral manifestations of defects in cholesterol or lipoprotein homeostasis.
Journal ArticleDOI

Protein Sensors for Membrane Sterols

TL;DR: Recent advances that explain how cells employ an ensemble of membrane-embedded proteins to monitor sterol concentrations and adjust sterol synthesis and uptake are discussed.
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