Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis.

Abstract:

:Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.

authors

Voskuhl RR,Itoh N,Tassoni A,Matsukawa MA,Ren E,Tse V,Jang E,Suen TT,Itoh Y

doi

10.1073/pnas.1821306116

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

10130-10139

issue

20

eissn

0027-8424

issn

1091-6490

pii

1821306116

journal_volume

116

pub_type

杂志文章
  • Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization.

    abstract::Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous pote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1407730111

    authors: Gajan D,Bornet A,Vuichoud B,Milani J,Melzi R,van Kalkeren HA,Veyre L,Thieuleux C,Conley MP,Grüning WR,Schwarzwälder M,Lesage A,Copéret C,Bodenhausen G,Emsley L,Jannin S

    更新日期:2014-10-14 00:00:00

  • Endoplasmic reticulum localization of the low density lipoprotein receptor mediates presecretory degradation of apolipoprotein B.

    abstract::Mutations in the low density lipoprotein (LDL) receptor (LDLR) cause hypercholesterolemia because of inefficient LDL clearance from the circulation. In addition, there is a paradoxical oversecretion of the metabolic precursor of LDL, very low density lipoprotein (VLDL). We recently demonstrated that the LDLR mediates ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.072557199

    authors: Gillian-Daniel DL,Bates PW,Tebon A,Attie AD

    更新日期:2002-04-02 00:00:00

  • Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists.

    abstract::Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource enviro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1073/pnas.1717522115

    authors: Urlacher SS,Ellison PT,Sugiyama LS,Pontzer H,Eick G,Liebert MA,Cepon-Robins TJ,Gildner TE,Snodgrass JJ

    更新日期:2018-04-24 00:00:00

  • Glutathione-mediated destabilization in vitro of [2Fe-2S] centers in the SoxR regulatory protein.

    abstract::SoxR is a transcription factor that governs a global defense against the oxidative stress caused by nitric oxide or excess superoxide in Escherichia coli. SoxR is a homodimer containing a pair of [2Fe-2S] clusters essential for its transcriptional activity, and changes in the stability of these metal centers could con...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.18.9449

    authors: Ding H,Demple B

    更新日期:1996-09-03 00:00:00

  • Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells.

    abstract::The type of cytokines produced during T cell responses determines susceptibility or resistance to many pathogens and influences the development of autoimmunity and allergy. To define the role of individual accessory molecules in cytokine production during primary immune responses, Drosophila cell lines expressing muri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.6.3023

    authors: Luksch CR,Winqvist O,Ozaki ME,Karlsson L,Jackson MR,Peterson PA,Webb SR

    更新日期:1999-03-16 00:00:00

  • Myocardin is required for cardiomyocyte survival and maintenance of heart function.

    abstract::Despite intense investigation over the past century, the molecular mechanisms that regulate maintenance and adaptation of the heart during postnatal development are poorly understood. Myocardin is a remarkably potent transcriptional coactivator expressed exclusively in cardiac myocytes and smooth muscle cells during p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910749106

    authors: Huang J,Min Lu M,Cheng L,Yuan LJ,Zhu X,Stout AL,Chen M,Li J,Parmacek MS

    更新日期:2009-11-03 00:00:00

  • Roles of calcium, serum, plasma, and folic acid in the control of proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts.

    abstract::In a culture medium of pH 7.4 and a folic acid concentration of 100 mug/liter that contains 5% heat-inactivated chicken plasma rather than serum, the rate of proliferation of normal chicken fibroblasts is determined by the concentration of calcium. Proliferation, rapid when the calcium concentration is physiological, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.3.675

    authors: Balk SD,Whitfield JF,Youdale T,Braun AC

    更新日期:1973-03-01 00:00:00

  • Low dielectric response in enzyme active site.

    abstract::The kinetics of charge transfer depend crucially on the dielectric reorganization of the medium. In enzymatic reactions that involve charge transfer, atomic dielectric response of the active site and of its surroundings determines the efficiency of the protein as a catalyst. We report direct spectroscopic measurements...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.050316997

    authors: Mertz EL,Krishtalik LI

    更新日期:2000-02-29 00:00:00

  • Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis.

    abstract::Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeabi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1008816107

    authors: Lu C,Diehl SA,Noubade R,Ledoux J,Nelson MT,Spach K,Zachary JF,Blankenhorn EP,Teuscher C

    更新日期:2010-11-02 00:00:00

  • Inhibitor-binding mode of homobelactosin C to proteasomes: new insights into class I MHC ligand generation.

    abstract::Most class I MHC ligands are generated from the vast majority of cellular proteins by proteolysis within the ubiquitin-proteasome pathway and are presented on the cell surface by MHC class I molecules. Here, we present the crystallographic analysis of yeast 20S proteasome in complex with the inhibitor homobelactosin C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0600647103

    authors: Groll M,Larionov OV,Huber R,de Meijere A

    更新日期:2006-03-21 00:00:00

  • Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling.

    abstract::Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson's disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA-deficient Drosophila exhibits defects ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1902958116

    authors: Mori A,Hatano T,Inoshita T,Shiba-Fukushima K,Koinuma T,Meng H,Kubo SI,Spratt S,Cui C,Yamashita C,Miki Y,Yamamoto K,Hirabayashi T,Murakami M,Takahashi Y,Shindou H,Nonaka T,Hasegawa M,Okuzumi A,Imai Y,Hattori N

    更新日期:2019-10-08 00:00:00

  • Fusigenic viral liposome for gene therapy in cardiovascular diseases.

    abstract::To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 评论,杂志文章,评审

    doi:10.1073/pnas.93.21.11421

    authors: Dzau VJ,Mann MJ,Morishita R,Kaneda Y

    更新日期:1996-10-15 00:00:00

  • Turbulent diffusion phase transition is due to singular energy spectrum.

    abstract::The phase transition for turbulent diffusion, reported by Avellaneda and Majda [Avellaneda, M. & Majda, A. J. (1994) Philos. Trans. R. Soc. London A 346, 205-233, and several earlier papers], is traced to a modeling assumption in which the energy spectrum of the turbulent fluid is singularly dependent on the viscosity...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.24.11005

    authors: Wallstrom TC

    更新日期:1995-11-21 00:00:00

  • Structural evolution of p53, p63, and p73: implication for heterotetramer formation.

    abstract::Oligomerization of members of the p53 family of transcription factors (p53, p63, and p73) is essential for their distinct functions in cell-cycle control and development. To elucidate the molecular basis for tetramer formation of the various family members, we solved the crystal structure of the human p73 tetramerizat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905867106

    authors: Joerger AC,Rajagopalan S,Natan E,Veprintsev DB,Robinson CV,Fersht AR

    更新日期:2009-10-20 00:00:00

  • Evaporation-induced cavitation in nanofluidic channels.

    abstract::Cavitation, known as the formation of vapor bubbles when liquids are under tension, is of great interest both in condensed matter science as well as in diverse applications such as botany, hydraulic engineering, and medicine. Although widely studied in bulk and microscale-confined liquids, cavitation in the nanoscale ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1014075109

    authors: Duan C,Karnik R,Lu MC,Majumdar A

    更新日期:2012-03-06 00:00:00

  • Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation.

    abstract::There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0707741104

    authors: Shaw P,Eckstrand K,Sharp W,Blumenthal J,Lerch JP,Greenstein D,Clasen L,Evans A,Giedd J,Rapoport JL

    更新日期:2007-12-04 00:00:00

  • Nerve growth factor: activation of the classical complement pathway by specific substitution for component C1-.

    abstract::The interaction of homogeneous preparations of mouse submandibular gland nerve growth factor (NGF) with the classical complement pathway was studied. NGF was found to be capable of carrying out the enzyme activities of the first component (C1-) of the classical complement pathway (i.e., the cleavage of zymogen C4 and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.8.2519

    authors: Boyle MD,Young M

    更新日期:1982-04-01 00:00:00

  • (2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

    abstract::(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.15.4609

    authors: Etienne-Smekens M,Vandenbussche P,Content J,Dumont JE

    更新日期:1983-08-01 00:00:00

  • Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells.

    abstract::Branched polyethylenimine (PEI) chains with an average molecular mass of 2 kDa (PEI2) have been covalently attached to gold nanoparticles (GNPs), and the potency of the resulting PEI2-GNPs conjugates as vectors for the delivery of plasmid DNA into monkey kidney (COS-7) cells in the presence of serum in vitro has been ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1233634100

    authors: Thomas M,Klibanov AM

    更新日期:2003-08-05 00:00:00

  • beta2-chimaerin is a novel target for diacylglycerol: binding properties and changes in subcellular localization mediated by ligand binding to its C1 domain.

    abstract::The members of the chimaerin family of Rac-GTPase-activating proteins possess a single C1 domain with high homology to those present in protein kinase C (PKC) isozymes. This domain in PKCs is involved in phorbol ester and diacylglycerol (DAG) binding. We previously have demonstrated that one of the chimaerin isoforms,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.21.11854

    authors: Caloca MJ,Garcia-Bermejo ML,Blumberg PM,Lewin NE,Kremmer E,Mischak H,Wang S,Nacro K,Bienfait B,Marquez VE,Kazanietz MG

    更新日期:1999-10-12 00:00:00

  • Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors.

    abstract::Contact-dependent growth inhibition (CDI) is a mechanism by which bacteria exchange toxins via direct cell-to-cell contact. CDI systems are distributed widely among Gram-negative pathogens and are thought to mediate interstrain competition. Here, we describe tsf mutations that alter the coiled-coil domain of elongatio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619273114

    authors: Jones AM,Garza-Sánchez F,So J,Hayes CS,Low DA

    更新日期:2017-03-07 00:00:00

  • Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos.

    abstract::The introduction of foreign genes into early mouse embryos and embryonic stem (ES) cells is invaluable for the analysis of gene function and regulation in the living animal. The use of vectors derived from retroviruses as gene transfer vehicles in this setting has had limited success because of silencing of transgene ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.251682798

    authors: Pfeifer A,Ikawa M,Dayn Y,Verma IM

    更新日期:2002-02-19 00:00:00

  • Dual control of cell growth by somatomedins and platelet-derived growth factor.

    abstract::Quiescent BALB/c 3T3 cells exposed briefly to a platelet-derived growth factor (PDGF) become "competent" to replicate their DNA but do not "progress" into S phase unless incubated with growth factors contained in platelet-poor plasma. Plasma from hypophysectomized rats is deficient in progression activity; it does not...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.3.1279

    authors: Stiles CD,Capone GT,Scher CD,Antoniades HN,Van Wyk JJ,Pledger WJ

    更新日期:1979-03-01 00:00:00

  • Organ-specific transcripts of different size and abundance derive from the same pyruvate, orthophosphate dikinase gene in maize.

    abstract::Analyses of genomic DNA and clones indicate that the pyruvate, orthophosphate dikinase (PPDK; ATP: pyruvate, orthophosphate phosphotransferase, EC 2.7.9.1) gene family of maize (Zea mays L. subsp. mays, line B73) contains two members. Restriction site and DNA sequence comparisons between PPDK genomic and leaf cDNA clo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.8.3004

    authors: Glackin CA,Grula JW

    更新日期:1990-04-01 00:00:00

  • Regulation of T cell activation and tolerance by PDL2.

    abstract::T cell activation and tolerance are regulated by costimulatory molecules. Although PD-1 serves as a crucial negative regulator of T cells, the function of its ligands, PDL1 and PDL2, is still controversial. In this study, we created a PDL2-deficient mouse to characterize its function in T cell activation and tolerance...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0601347103

    authors: Zhang Y,Chung Y,Bishop C,Daugherty B,Chute H,Holst P,Kurahara C,Lott F,Sun N,Welcher AA,Dong C

    更新日期:2006-08-01 00:00:00

  • Targeting the stromal androgen receptor in primary prostate tumors at earlier stages.

    abstract::To differentiate roles of androgen receptor (AR) in prostate stromal and epithelial cells, we have generated inducible-(ind)ARKO-TRAMP and prostate epithelial-specific ARKO TRAMP (pes-ARKO-TRAMP) mouse models, in which the AR was knocked down in both prostate epithelium and stroma or was knocked out in the prostate ep...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804701105

    authors: Niu Y,Altuwaijri S,Yeh S,Lai KP,Yu S,Chuang KH,Huang SP,Lardy H,Chang C

    更新日期:2008-08-26 00:00:00

  • Correction of proximal tubule phosphate transport defect in Hyp mice in vivo and in vitro with indomethacin.

    abstract::X-linked hypophosphatemia is the most prevalent inherited form of rickets. In this disorder, rickets results from hyperphosphaturia and inappropriately normal levels of 1,25(OH)2-vitamin D. Current therapy with oral phosphate and vitamin D improves the rickets, but has significant morbidity and does not significantly ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1834060100

    authors: Baum M,Loleh S,Saini N,Seikaly M,Dwarakanath V,Quigley R

    更新日期:2003-09-16 00:00:00

  • Specific interaction of mutant p53 with regions of matrix attachment region DNA elements (MARs) with a high potential for base-unpairing.

    abstract::Mutant, but not wild-type p53 binds with high affinity to a variety of MAR-DNA elements (MARs), suggesting that MAR-binding of mutant p53 relates to the dominant-oncogenic activities proposed for mutant p53. MARs recognized by mutant p53 share AT richness and contain variations of an AATATATTT "DNA-unwinding motif," w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.23.13681

    authors: Will K,Warnecke G,Wiesmüller L,Deppert W

    更新日期:1998-11-10 00:00:00

  • Trans/cis (Z/E) photoisomerization of the chromophore of photoactive yellow protein is not a prerequisite for the initiation of the photocycle of this photoreceptor protein.

    abstract::The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic acid) has been replaced by an analogue with a triple bond, rather than a double bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding hybrid I) and by a "locked" chromophore (through reconstitution with 7-hydroxycoumari...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7396

    authors: Cordfunke R,Kort R,Pierik A,Gobets B,Koomen GJ,Verhoeven JW,Hellingwerf KJ

    更新日期:1998-06-23 00:00:00

  • Effects of glycyl-L-glutamine and methylprednisolone on maintenance of acetylcholinesterase of transected rat sciatic nerves.

    abstract::Under anesthesia with sodium pentobarbital, the sciatic nerves of rats were transected bilaterally, and a catheter was inserted into the central end of the left renal artery. After an initial flush, an Alzet pump was attached to the catheter, containing various concentrations of glycyl-L-glutamine (Gly-Gln), methylpre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.23.9495

    authors: Koelle GB,Han MS

    更新日期:1990-12-01 00:00:00