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2012 ; 2
(1
): 76-103
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Oxysterols and their cellular effectors
#MMPMID24970128
Olkkonen VM
; Béaslas O
; Nissilä E
Biomolecules
2012[Feb]; 2
(1
): 76-103
PMID24970128
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Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of
cholesterol biosynthesis, with a spectrum of biologic activities. Several
oxysterols have cytotoxic and pro-apoptotic activities, the ability to interfere
with the lateral domain organization, and packing of membrane lipids. These
properties may account for their suggested roles in the pathology of diseases
such as atherosclerosis, age-onset macular degeneration and Alzheimer's disease.
Oxysterols also have the capacity to induce inflammatory responses and play roles
in cell differentiation processes. The functions of oxysterols as intermediates
in the synthesis of bile acids and steroid hormones, and as readily transportable
forms of sterol, are well established. Furthermore, their actions as endogenous
regulators of gene expression in lipid metabolism via liver X receptors and the
Insig (insulin-induced gene) proteins have been investigated in detail. The
cytoplasmic oxysterol-binding protein (OSBP) homologues form a group of
oxysterol/cholesterol sensors that has recently attracted a lot of attention.
However, their mode of action is, as yet, poorly understood. Retinoic acid
receptor-related orphan receptors (ROR) ? and ?, and Epstein-Barr virus induced
gene 2 (EBI2) have been identified as novel oxysterol receptors, revealing new
physiologic oxysterol effector mechanisms in development, metabolism, and
immunity, and evoking enhanced interest in these compounds in the field of
biomedicine.
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