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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Panzenboeck, U; Andersson, U; Hansson, M; Sattler, W; Meaney, S; Björkhem, I.
On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis.
J Lipid Res. 2007; 48(5): 1167-1174. Doi: 10.1194/jlr.M700027-JLR200 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Panzenboeck Ute
Co-Autor*innen der Med Uni Graz
Sattler Wolfgang
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Abstract:
The most serious consequence of sterol 27-hydroxylase deficiency in humans [cerebrotendinous xanthomatosis (CTX)] is the development of cholestanol-containing brain xanthomas. The cholestanol in the brain may be derived from the circulation or from 7alpha-hydroxylated intermediates in bile acid synthesis, present at 50- to 250-fold increased levels in plasma. Here, we demonstrate a transfer of 7alpha-hydroxy-4-cholesten-3-one across cultured porcine brain endothelial cells (a model for the blood-brain barrier) that is approximately 100-fold more efficient than the transfer of cholestanol. Furthermore, there was an efficient conversion of 7alpha-hydroxy-4-cholesten-3-one to cholestanol in cultured neuronal and glial cells as well as in monocyte-derived macrophages of human origin. It is concluded that the continuous intracellular production of cholestanol from a bile acid precursor capable of rapidly passing biomembranes, including the blood-brain barrier, is likely to be of major importance for the accumulation of cholestanol in patients with CTX. Such a mechanism also fits well with the observation that treatment with chenodeoxycholic acid, which normalizes the level of the bile acid precursor, results in a reduction of cholestanol-containing xanthomas even in the brain.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Brain - metabolism
Cell Differentiation - metabolism
Cells, Cultured - metabolism
Cholestanol - chemistry
Endothelial Cells - metabolism
Humans - metabolism
Macrophages - cytology
Molecular Structure - cytology
Neuroglia - metabolism
Neurons - metabolism
Swine - metabolism
Xanthomatosis, Cerebrotendinous - metabolism

Find related publications in this database (Keywords)
blood-brain barrier
brain xanthomas
brain endothelial cells
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