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We have recently reported significantly reduced levels of the mRNA of genes critical for the cholesterol biosynthesis pathway in the brains of mice and patients with Huntington's disease (HD), which are indicative of a biological dysfunction. We here show that the brains of R6/2 transgenic mice have progressively decreasing levels of the cholesterol(More)
Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in(More)
OBJECTIVES Cholesterol has been linked to Alzheimer's disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and(More)
Our recent analyses of the cholesterol biosynthetic pathway in Huntington's disease (HD) cells, in the R6/2 huntingtin-fragment mouse model of HD as well as in human tissues have provided the first evidence of altered activity of this pathway in genetically identifiable HD samples. Here we report that these changes also occur in the full-length-huntingtin(More)
In the central nervous system cholesterol is involved in membrane structure and function. Since the blood-brain barrier efficiently prevents cholesterol uptake from the circulation, de novo synthesis is responsible for almost all cholesterol present there. In mature brain neurons down regulate their cholesterol synthesis and rely on delivery from ApoE(More)
In contrast to their parent molecule cholesterol, two of its side-chain oxidized metabolites are able to cross the blood-brain barrier. There is a concentration-driven flux of 24S-hydroxycholesterol (24S-OHC) from the brain into the circulation, which is of major importance for elimination of excess cholesterol from the brain. The opposite flux of(More)
The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain(More)
OBJECTIVE The objective of this study was to assess the relationship between active smoking as well as environmental tobacco smoke (ETS) exposure and severe small for gestational age (SGA) at term in a sample of pregnant Italian women. METHODS A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of(More)
A number of sentinels sense incoming herpes simplex virus (HSV) virions and initiate an immediate innate response. The first line of defense at the cell surface is TLR2 (Toll-like receptor 2), whose signature signaling activity leads to activation of the key transcription factor NF-κB. We report that the HSV pathogen-associated molecular patterns for TLR2(More)
Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways(More)