The role of apolipoprotein E in lipid metabolism in the central nervous system

Han, Xianlin

doi:10.1007/s00018-004-4009-z

Cited by 67 publications

(53 citation statements)

References 109 publications

(118 reference statements)

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“…ApoE plays a prominent role in the transport and metabolism of plasma cholesterol and TG through its ability to interact with the low density lipoprotein (LDL) receptor and the LDL receptor-related protein (32,33). However, such a role of apoE in the CNS is uncertain, but many studies demonstrated that apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, although apoE may modulate cholesterol and phospholipid homeostasis in selective subcellular membrane compartments (34). In contrast to such a uncertainty, it has been demonstrated that apoE mediates sulfatide trafficking and metabolism in the CNS (35) and the PNS (Cheng, Jiang and Han, unpublished data).…”

Section: Some Proteins Related To Lipids Play Different Roles In the mentioning

confidence: 99%

Neurolipidomics: challenges and developments

Han

2007

Front Biosci

101

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The field of lipidomics is one of the most rapidly expanding areas of systems biology research. Considering the uniqueness and complexity of the lipidome in the nervous system (i.e., neurolipidome), neurolipidomics remains quite challenging but exciting. With the recent development of mass spectrometry (MS)-based lipidomics, particularly the rapid improvement of multi-dimensional MS-based shotgun lipidomics, much progress has been made in neurolipidomics. As the accelerated development of future technologies enables lipidomics penetrance into lower and lower abundance regions of mass contents of individual lipid molecular species, it can be anticipated that many biochemical mechanisms underlying lipid metabolism critical to neuronal disease states will be increasingly uncovered. Through exploiting the information content inherent in the complexity of neuronal lipid composition and kinetic turnover which can be revealed by neurolipidomics, substantial insights into neuronal plasticity and gene function can be gathered. Through neurolipidomics, the markers for these neuronal diseases which identify pathological alterations and are diagnostic of disease onset, progression or severity may potentially be discovered. Accordingly, with neurolipidomics, our understanding of the complexities of the nervous system will be undoubtedly accelerated, as many mysteries are resolved.

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Section: Some Proteins Related To Lipids Play Different Roles In the mentioning

confidence: 99%

Neurolipidomics: challenges and developments

Han

2007

Front Biosci

101

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“…ApoE has been reported to carry out additional functions such as stimulation of cholesterol efflux from macrophages, prevention of platelet aggregation, and inhibition of proliferation of T-lymphocyte and endothelial cells. Its common structural isoforms differentially affect the risk of developing atherosclerosis and neurodegenerative disorders, including Alzheimers's disease (reviewed in Han, 2004;Greenow et al, 2005).…”

Section: Intestine and Miscellaneous Expressionmentioning

confidence: 99%

Xenopus cDNA microarray identification of genes with endodermal organ expression

Park

Hayata

Cho

et al. 2007

Developmental Dynamics

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The endoderm is classically defined as the innermost layer of three Metazoan germ layers. During organogenesis, the endoderm gives rise to the digestive and respiratory tracts as well as associated organs such as the liver, pancreas, and lung. At present, however, how the endoderm forms the variety of cell types of digestive and respiratory tracts as well as the budding organs is not well understood. In order to investigate the molecular basis and mechanism of organogenesis and to identify the endodermal organ-related marker genes, we carried out microarray analysis using Xenopus cDNA chips. To achieve this goal, we isolated the Xenopus gut endoderm from three different stages of Xenopus organogenesis, and separated each stage of gut endoderm into anterior and posterior regions. Competitive hybridization of cDNA between the anterior and posterior endoderm regions, to screen genes that specifically expressed in the major organs, revealed 915 candidates. We then selected 104 clones for in situ hybridization analysis. Here, we report the identification and expression patterns of the 104 Xenopus endodermal genes, which would serve as useful markers for studying endodermal organ development.

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“…Although the delivery of plasma lipoproteins from the circulation to the CNS is precluded by the blood-brain barrier, the CNS contains a distinct population of high-density lipoproteins that are secreted by glia and contain apolipoprotein E (apoE) as their major apolipoprotein (Han, 2004). ApoE is thought to play an important role in the CNS, because apoE synthesis increases dramatically after injury of either the CNS or peripheral nervous system (Ignatius et al, 1986;Mahley, 1988).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1

Hayashi¹,

Campenot²,

Vance³

et al. 2007

J. Neurosci.

150

151

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Apolipoprotein E (apoE)-containing lipoproteins (LPs) are secreted by glia and play important roles in lipid homeostasis in the CNS. Glia-derived LPs also promote synaptogenesis and stimulate axon growth of CNS neurons. Here, we provide evidence that glia-derived LPs protect CNS neurons from apoptosis by a receptor-mediated signaling pathway. The protective effect was greater for apolipoprotein E3 than for apolipoprotein E4, the expression of which is a risk factor for Alzheimer's disease. The anti-apoptotic effect of LPs required the association of apolipoprotein E with lipids but did not require cholesterol. Apoptosis was not prevented by lipids alone or by apoA1-or apoJ-containing lipoproteins. The prevention of neuronal apoptosis was initiated after the binding of LPs to the low-density lipoprotein receptor-related protein (LRP), a multifunctional receptor of the low-density lipoprotein receptor family. We showed that inhibition of LRP activation, by treatment of neurons with receptor-associated protein or anti-LRP antibodies, or by LRP gene-silencing experiments, reduced the protective effect of LPs. Furthermore, another LRP ligand, ␣ 2 -macroglobulin, also protected the neurons from apoptosis. After binding to LRP, LPs initiate a signaling pathway that involves activation of protein kinase C␦ and inactivation of glycogen synthase kinase-3␤. These findings indicate the potential for using glial lipoproteins or an activator of the LRP signaling pathway for treatment for neurodegenerative disorders such as Alzheimer's disease.

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The role of apolipoprotein E in lipid metabolism in the central nervous system

Cited by 67 publications

References 109 publications

Neurolipidomics: challenges and developments

Neurolipidomics: challenges and developments

Xenopus cDNA microarray identification of genes with endodermal organ expression

Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1

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