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Cholesterol metabolism and homeostasis in the brain.

Zhang J, Liu Q - Protein Cell (2015)

Bottom Line: The content of cholesterol in brain must be accurately maintained in order to keep brain function well.The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood.This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, and School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China.

ABSTRACT
Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

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Related in: MedlinePlus

Cholesterol synthesis and metabolism in the brain. Cholesterol in neurons is primarily biosynthesized through Kandutsch-Russell pathway, whereas in astrocytes through Bloch pathway. Adult neurons essentially rely on astrocyte for cholesterol providing. Cholesterol uptake is via LRP1/LDLR receptors as apoE-containing cholesterol form. It is then converted to free cholesterol in endosome/lysosome in assistance of NPC1 and NPC2. Excess of cholesterol is prevented by intracellular esterification and storage in lipid droplets, or released as a complex with apolipoprotein-containing lipoprotein via ATP-binding cassette transporter, or converting to oxysterols then passing through BBB
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Related In: Results  -  Collection


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Fig1: Cholesterol synthesis and metabolism in the brain. Cholesterol in neurons is primarily biosynthesized through Kandutsch-Russell pathway, whereas in astrocytes through Bloch pathway. Adult neurons essentially rely on astrocyte for cholesterol providing. Cholesterol uptake is via LRP1/LDLR receptors as apoE-containing cholesterol form. It is then converted to free cholesterol in endosome/lysosome in assistance of NPC1 and NPC2. Excess of cholesterol is prevented by intracellular esterification and storage in lipid droplets, or released as a complex with apolipoprotein-containing lipoprotein via ATP-binding cassette transporter, or converting to oxysterols then passing through BBB

Mentions: Different profiles of post-squalene precursors were observed in neurons in comparison to astrocytes (Fig. 1). Neurons contain mainly sterols of Kandutsch-Russel pathway, including precursors lanosterol (LA), 7-dehydrocholesterol (7D), and lathosterol (LT) whereas astrocytes contain precursors of the Bloch pathway, such as desmosterol (DE) (Nieweg et al., 2009). In adult neurons, radioactive label was mainly found in lanosterol, whereas in glial cells it accumulated predominantly in cholesterol (Nieweg et al., 2009). A very low level of lanosterol-converting enzymes-24-dehudrocholesterol reductase (DHCR24) and lanosterol 14-alpha demethulase (CYP51) were detected in adult neurons, indicating that neurons have difficulty converting lanosterol efficiently. It was detected that adult neurons have a lower rate of sterol synthesis in comparison to glial cells. All the evidences demonstrate that adult neurons have a lower capacity to compensate for a cholesterol deficit by de novo synthesis in comparison to astrocytes. However, in situ hybridization data from the Allen Mouse Brain Atlas suggest that transcript level of many cholesterol synthesis enzymes are higher in neurons compared to these in astrocytes (Valdez et al., 2010), although higher transcript level doesn’t necessarily mean the actual protein level and enzymatic activity have the same pattern. Compartmented culture studies showed that in neurons, cholesterol synthesis is restricted to neuronal somata and does not occur in axons, but phospholipids formation takes place in both compartments, newly synthesized cholesterol in neurons is transported from soma to axon (Vance et al., 1994).Figure 1


Cholesterol metabolism and homeostasis in the brain.

Zhang J, Liu Q - Protein Cell (2015)

Cholesterol synthesis and metabolism in the brain. Cholesterol in neurons is primarily biosynthesized through Kandutsch-Russell pathway, whereas in astrocytes through Bloch pathway. Adult neurons essentially rely on astrocyte for cholesterol providing. Cholesterol uptake is via LRP1/LDLR receptors as apoE-containing cholesterol form. It is then converted to free cholesterol in endosome/lysosome in assistance of NPC1 and NPC2. Excess of cholesterol is prevented by intracellular esterification and storage in lipid droplets, or released as a complex with apolipoprotein-containing lipoprotein via ATP-binding cassette transporter, or converting to oxysterols then passing through BBB
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383754&req=5

Fig1: Cholesterol synthesis and metabolism in the brain. Cholesterol in neurons is primarily biosynthesized through Kandutsch-Russell pathway, whereas in astrocytes through Bloch pathway. Adult neurons essentially rely on astrocyte for cholesterol providing. Cholesterol uptake is via LRP1/LDLR receptors as apoE-containing cholesterol form. It is then converted to free cholesterol in endosome/lysosome in assistance of NPC1 and NPC2. Excess of cholesterol is prevented by intracellular esterification and storage in lipid droplets, or released as a complex with apolipoprotein-containing lipoprotein via ATP-binding cassette transporter, or converting to oxysterols then passing through BBB
Mentions: Different profiles of post-squalene precursors were observed in neurons in comparison to astrocytes (Fig. 1). Neurons contain mainly sterols of Kandutsch-Russel pathway, including precursors lanosterol (LA), 7-dehydrocholesterol (7D), and lathosterol (LT) whereas astrocytes contain precursors of the Bloch pathway, such as desmosterol (DE) (Nieweg et al., 2009). In adult neurons, radioactive label was mainly found in lanosterol, whereas in glial cells it accumulated predominantly in cholesterol (Nieweg et al., 2009). A very low level of lanosterol-converting enzymes-24-dehudrocholesterol reductase (DHCR24) and lanosterol 14-alpha demethulase (CYP51) were detected in adult neurons, indicating that neurons have difficulty converting lanosterol efficiently. It was detected that adult neurons have a lower rate of sterol synthesis in comparison to glial cells. All the evidences demonstrate that adult neurons have a lower capacity to compensate for a cholesterol deficit by de novo synthesis in comparison to astrocytes. However, in situ hybridization data from the Allen Mouse Brain Atlas suggest that transcript level of many cholesterol synthesis enzymes are higher in neurons compared to these in astrocytes (Valdez et al., 2010), although higher transcript level doesn’t necessarily mean the actual protein level and enzymatic activity have the same pattern. Compartmented culture studies showed that in neurons, cholesterol synthesis is restricted to neuronal somata and does not occur in axons, but phospholipids formation takes place in both compartments, newly synthesized cholesterol in neurons is transported from soma to axon (Vance et al., 1994).Figure 1

Bottom Line: The content of cholesterol in brain must be accurately maintained in order to keep brain function well.The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood.This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, and School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China.

ABSTRACT
Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

Show MeSH
Related in: MedlinePlus