NOTEWORTHY ARTICLES 2002/2003

Neurobiology of Lipids 'Noteworthy' section alerts you about the selected noteworthy original research (not review) articles and meeting reports (published in other journals) on the subject of the Neurobiology of Lipids scope.

The reference to each article may be accompanied by the referee name (a member of the Neurobiology of Lipids editorial board or a journal reader), the authors' key note comments, the date of the 'noteworthy' alert, and NoL letter to editor, and links to related articles (if any).

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NOTEWORTHY 2004

SUBMIT LETTER2EDITOR

PUBMED SEARCH

HIGHWIRE SEARCH

NoL PATENTS

Generation of Viable Cholesterol-Free Mice.
Wechsler A, Brafman A, Shafir M, Heverin M, Gottlieb H, Damari G, Gozlan-Kelner S, Spivak I, Moshkin O, Fridman E, Becker Y, Skaliter R, Einat P, Faerman A, Björkhem I, Feinstein E.
Science 19 Dec 2003 302(5653): 2087.
[FullText] [Authors company press release] [Authors contact]

selected by Alexei Koudinov

Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice.
Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL
J Lip Res 2003 44(11): 2109-19.
[PubMed] [Authors contact]

selected by Temirbolat Berezov

Dynamics of membrane lipid domains in neuronal cells differentiated in culture.
Ottico E, Prinetti A, Prioni S, Giannotta C, Basso L, Chigorno V, Sonnino S
J Lip Res 2003 44(11): 2142-52.
[PubMed] [Authors contact]

selected by Alexei Koudinov

Association of aortic atherosclerosis with cerebral b-amyloidosis and learning deficits in a mouse model of Alzheimer's disease
Li L, Cao D, Garber DW, Kim H, Fukuchi K-i
Am J Pathol 2003 163(6): 2155-64.
[PubMed] [ FullText ] [Authors contact]
 

Keynote by Ling Li: "By establishing a mouse model prone to both atherosclerosis and b-amyloidosis, we have shown for the first time that aortic atherosclerosis correlates positively with cerebral b-amyloidosis and that an atherogenic diet is associated with exacerbated spatial learning deficits in APP transgenic mice. Our data demonstrated that overexpression of a mutant form of APP initiates and/or promotes the development of atherosclerosis in a susceptible mouse strain, suggesting a causative role of APP and/or its derivatives in the etiology of atherosclerosis. These findings warrant further investigations of mechanisms by which b-amyloidosis and atherosclerosis are connected, in particular, investigation of the roles of Ab and APP in atherogenesis."

selected by Alexei Koudinov

Plasma lipid levels in Alzheimer's disease patients treated by Donepezil hydrochloride: a cross-sectional study.
Adunsky A, Chesnin V, Ravona R, Harats D, Davidson M
Arch Gerontol Geriatr Jan-Feb 2004 38(1): 61-8.
[PubMed] [Authors contact]

selected by Alexei Koudinov

Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans.
Lesa GM, Palfreyman M, Hall DH, Clandinin MT, Rudolph C, Jorgensen EM, Schiavo G.
J Cell Sci 2003 116(24): 4965-67.
[PubMed] [ Journal issue article preview ] [Related NoL: 1 ] [Authors contact]
 

Keynote by Giovanni Lesa: "This paper demonstrates that mutant C. elegans animals lacking long-chain polyunsaturated fatty acids (LC-PUFAs) are defective in neurotransmitter release. Using a combination of molecular genetic and pharmacological techniques, we show that LC-PUFAs are specifically required in both serotonergic and cholinergic neurons for their efficient function. Electrophysiological studies reveal that the neuronal defects displayed by LC-PUFA-deficient animals are caused by a decrease in neurotransmitter release. Finally, ultrastructural analysis of synaptic terminals shows that synapses are depleted of synaptic vesicles. Thus, LC-PUFAs are required to maintain a number of synaptic vesicles at presynaptic sites sufficient to support normal neurotransmission."

selected by Alexei Koudinov

Atorvastatin-induced polyneuropathy.
Silverberg C
Ann Intern Med 2003 139(9): 792-3.
[PubMed] [FullText] [Related articles: 1 ] [Author contact]

selected by Alexei Koudinov

Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage.
Kay A, Petzold A, Kerr M, Keir G, Thompson E, Nicoll J.
Stroke 6 Nov 2003 (ePub ahead of print) doi: 10.1161/01.STR.0000100157.88508.2F
[Abstract/FullText] [Related articles: 1 | 2 ] [Authors contact]

selected by Alexei Koudinov

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects.
Steffens DC, Trost WT, Payne ME, Hybels CF, and MacFall JR
Biol Psych 1 Oct 2003 54(7): 674-681.
[PubMed] [ FullText at Science Direct ] [Related articles: 1 | 2 ] [Authors contact]

selected by Ilya Reznik

The apolipoprotein E e4 allele and antidepressant efficacy in cognitively intact elderly depressed patients.
Greer M. Murphy GM Jr, Kremer C, Rodrigues H, Schatzberg AF, and Mirtazapine versus Paroxetine Study Group
Biol Psych 1 Oct 2003 54(7): 665-673.
[PubMed] [ FullText at Science Direct ] [Related articles: 1 | 2 ] [Authors contact]

selected by Ilya Reznik

Local regulation of fat metabolism in peripheral nerves.
Verheijen M.H.G, Chrast R, Burrola P, Lemke G.
Genes Dev. Oct 2003 17(19): 2450-64
[Abstract/FullText] [Authors contact]
 

Keynote by Mark Verheijen: "We performed microarray analyses using mRNAs isolated from developing mouse sciatic nerves. Unexpectedly, we found that many genes involved in lipid metabolism are maximally expressed in the mature nerve, after the myelination of axons by Schwann cells is completed; most of these late-onset genes are expressed by adipocytes, which make up the bulk of the epineurium. However, several genes, including SREBP-1, SREBP-2 and Lpin1, are also expressed in the endoneurium. Most interestingly, we found that Lpin1 null mutations lead to lipoatrophy of the epineurium, and to the dysregulation of a battery of genes required for the regulation of storage lipid metabolism in both the endoneurium and peri/epineurium. Together with the observation that these mutations also result in peripheral neuropathy, our findings demonstrate a crucial role for local storage lipid metabolism in mature peripheral nerve function."

selected by Alexei Koudinov

Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease.
Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Bjorkhem J
J Lip Research 2004 45(1): p. 186-193 (ePub 1 Oct 2003) doi: 10.1194/jlr.M300320-JLR200
[Abstract/FullText] [Cited NoL article] [Authors contact]

selected by Alexei Koudinov

Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease.
Girardot N, Allinquant B, Langui D, Laquerriere A, Dubois B, Hauw JJ, Duyckaerts C
Neuropathol Appl Neurobiol Oct 2003 29(5): 451-461
[PubMed] [Authors contact]

selected by Alexei Koudinov

Exclusively targeting b-secretase to lipid rafts by GPI-anchor addition up-regulates b-site processing of the amyloid precursor protein.
Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ
Proc Natl Acad Sci USA 22 Sept 2003 (ePub ahead of print) doi:10.1073/pnas.1635130100
[Abstract/FullText] [ Related articles: 1 | 2 | 3 | 4 ] [Authors contact]
 

Keynote by Tony Turner: "This paper lends direct support to the hypothesis that cholesterol levels may correlate with amyloid peptide accumulation in the brain. The study shows that the initial step in forming the Abeta peptide, catalysed by beta-secretase (BACE), can be dramatically enhanced by guiding the beta-secretase into cholesterol- and glycosphingolipid rich raft domains in the membrane. This targeting of BACE was achieved by tagging the enzyme with a glycolipid (GPI) anchor. Cholesterol depletion reversed the enhancement in BACE activity. These data provide yet further evidence that lipid rafts may be a critical site for amyloid generation and that raised cholesterol levels are a risk factor for the development of Alzheimer's disease."

selected by Alexei Koudinov

Blockade of HMG-CoA reductase activity causes changes in microtubule-stabilizing protein tau via suppression of geranylgeranylpyrophosphate formation: implications for Alzheimer's disease.
Meske V, Albert F, Richter D, Schwarze J, Ohm TG
Eur J Neurosci Jan 2003 17(1): p. 93-102
[PubMed] [Authors contact]

selected by Luisa Diomede

Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice.
Harris FM, Brecht WJ, Xu Q, et al.
Proc Natl Acad Sci USA 25 Aug 2003 (ePub ahead of print) doi:10.1073/pnas.1434398100
[Abstract/FullText] [Related articles: 1 | 2 | 3 | 4 | 5 ] [Authors contact]

selected by Alexei Koudinov

Apolipoprotein E Genotype Predicts 24-Month Bayley Scales Infant Development Score.
Wright RO, et al.
Pediatr Res. 20 Aug 2003 (ePub ahead of print) doi: 10.1203/01.PDR.0000090927.53818.DE
[PubMed] [Abstract/FullText] [Authors contact]
 

Keynote by Robert Wright: "Among infants living in Mexico, apolipoprotein E4 genotype predicted improved performance on the 24 month infant mental developmental index score of the Bayley Scale of Infant development. The protective effect of the E4 allele may help to explain its high prevalence  worldwide, despite being associated with Alzheimer's Disease in post-reproductive years. The role of lipoproteins and cholesterol metabolism in infant development deserves further study."

selected by Alexei Koudinov

Reelin promotes peripheral synapse elimination and maturation.
Quattrocchi CC, et al.
Science 1 Aug 2003 301(5633): p. 649-53
[PubMed] [Abstract/FullText] [ Related articles: 1 | 2 | 3 ] [Authors contact]
 

Keynote by Gabriella D’Arcangelo: "A protein called Reelin is important for the cellular organization of the embryonic brain. Here we report that Reelin is also necessary for the maturation of the neuromuscular junction in the postnatal peripheral nervous system. In Reelin-deficient mice, these junctions are immature and innervated by multiple axons. Reelin, through its protease activity, prunes multiple axons and promotes their withdrawal. This work demonstrates that Reelin has several functions: one is to control neuronal positioning in the embryonic brain, the other is to refine connectivity between nerve cells and muscle fibers and, possibly, between brain cells."

selected by Alexei Koudinov

Autosomal recessive hypercholesterolemia protein interacts with and regulates the cell surface level of Alzheimer's amyloid beta precursor protein.
Noviello C, Vito P, Lopez P, Abdallah M, and D'Adamio L.
J Biol Chem Aug 2003 278(34): p. 31843-7
[PubMed] [Abstract/FullText] [Authors contact]

selected by Alexei Koudinov

Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts.
Eroglu S, Brügger B, Wieland F, and Sinning I.
Proc Natl Acad Sci USA 15 Aug 2003 (ePub ahead of print) doi:10.1073/pnas.1737042100
[Abstract/FullText] [Authors contact]

selected by Alexei Koudinov

High cholesterol affects platelet APP processing in controls and in AD patients.
Borroni B, Colciaghi F, Lenzi GL, Caimi L, Cattabeni F, Di Luca M, and Padovani A.
Neurobiol Aging Sept-Oct 2003 24(5): p. 631-6
[PubMed] [FullText] [Related articles: 1 | 2 ] [ Related NoLs: 1 | 2 | 3 ] [Authors contact]

selected by Alexei Koudinov

Trace amounts of copper in water induce b-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease.
Sparks DL and Schreurs BG.
Proc Natl Acad Sci USA 14 Aug 2003 (ePub ahead of print) doi:10.1073/pnas.1832769100
[ PubMed ] [Abstract/FullText] [Related articles: 1 ] [ Related NoLs: 1 | 2 | 3 ] [ Related News: 1 | 2 ] [Authors contact]

selected by Alexei Koudinov

Statin-associated memory loss: analysis of 60 case reports and review of the literature.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.
Pharmacotherapy July 2003 23(7): p. 871-80
[PubMed] [FullText] [Authors contact]

selected by Alexei Koudinov

Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology.
Pappolla MA, et al.
Neurology 22 July 2003 61: p. 199-205
[PubMed] [Correspondence] [Authors contact]

selected by Alexei Koudinov

The production of amyloid-beta peptide is a critical requirement for the viability of central neurons.
Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA.
J Neurosci. 2 July 2003 23(13): p. 5531-5
[PubMed] [Authors contact]

selected by Alexei Koudinov

Presenilin redistribution associated with aberrant cholesterol transport enhances b-amyloid production in vivo.
Burns M, Gaynor K, Olm V, Mercken M, LaFrancois J, Wang L, Mathews PM, Noble W, Matsuoka Y, Duff K.
J Neurosci. 2 July 2003 23(13): p. 5645-9
[PubMed] [Authors contact]

selected by Alexei Koudinov

Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann-Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease.
Treiber-Held S, Distl R, Meske V, Albert F, Ohm TG.
J Pathol. May 2003 200(1): p. 95-103
[PubMed]  [Related articles: 1 ] [Authors contact]

selected by Alexei Koudinov

Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration.
Xie C, Lund EG, Turley SD, Russell DW, Dietschy JM.
J Lip Res. 6 June 2003 (ePub ahead of print) doi:10.1194/jlr.M300164-JLR2003
[PubMed] [Authors contact]
 

Keynote by John Dietschy: "These studies were done to identify and quantitate the pathways for cholesterol turnover in the central nervous system.  In 7-week-old mice, 1.4 mg/kg body weight was excreted from the CNS each day.  Sixty-four percent of this excretion occured after 24-hydroxylation of the cholesterol molecule.  In a mouse model of neurodegeneration, total excretion increased to 2.3 mg/day per kg, but only 22 percent of this involved 24-hydroxylation.  Thus, at least two pathways are involved in cholesterol turnover in the brain, and in the presence of neurodegeneration the 24-hydroxylase-independent pathway predominates."

selected by Alexei Koudinov

Expression of LXR target genes decreases cellular amyloid beta peptide secretion.
Sun Y, Yao J, Kim TW, Tall AR.
J Biol Chem. 16 May 2003 (ePub ahead of print) doi: 10.1074/jbc.M300760200
[PubMed] [Authors contact]

selected by Alexei Koudinov

Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment.
Blalock EM, Chen KC, Sharrow K, Herman JP, Porter NM, Foster TC, Landfield PW.
J Neurosci. 1 May 2003 23: p. 3807-19
[PubMed] [Authors contact]

selected by Alexei Koudinov

Casting metal nanowires within discrete self-assembled peptide nanotubes.
Reches M, Gazit E.
Science. 25 April 2003 300: p. 625-7
[PubMed] [Authors contact]
 

Keynote by Ehud Gazit: "We demonstrated that the diphenylalanine core-recognitions motif of the beta-amyloid polypeptide can form stiff and elongated peptide nanotubes. The formation of extremely well-ordered structures by such a small peptide is consistent with our hypothesis on the role of aromatic interactions in many cases of amyloid fibrils formation. We suggested that aromatic interaction can provide both energetic contribution as well as order and directionality in the process of amyloid self-assembly due to their restricted binding geometry. The results are also consistent with the suggestion made by the late Nobel laureate Max Perutz in one of his very last articles, that amyloid fibrils are water-filled nanotubes."

selected by Alexei Koudinov

Determination of plasma membrane fluidity with a fluorescent analogue of sphingomyelin by FRAP measurement using a standard confocal microscope.
Klein C, Pillot T, Chambaz J, Drouet B.
Brain Res Brain Res Protoc. March 2003 11(1): p. 46-51
[PubMed] [Authors: contact | web site ]
 

Keynote by Christophe Klein: "Fluorescence Recovery After Photobleaching (FRAP) is a useful method to study the fluidity of plasma membranes. The availability of modern confocal microscopes makes this technique easy to use. In this paper we describe the protocol that we developed with a Zeiss LSM510 to measure the lateral diffusion of lipid in living cell membranes. As a test experiment, we measured the increase of diffusion of NBD-sphingomyelin upon cholesterol depletion induced by methyl-b-cyclodextrin. We successfully applied this method to study the effects of non-fibrillar Ab peptide on membrane fluidity (Sponne et al., J. Biol. Chem. 2003; 278:3437-3445)."

selected by Alexei Koudinov

Plasma vitamin C, cholesterol and homocysteine are associated with grey matter volume determined by MRI in non-demented old people.
Whalley LJ, Staff RT, Murray AD, Duthie SJ, Collins AR, Lemmon HA, Starr JM, Deary IJ.
Neurosci Lett. 8 May 2003 341(3): p. 173-6
[PubMed] [Authors contact]

selected by Alexei Koudinov

Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis.
Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG.
Science. 18 April 2003 300: p. 486-9
[PubMed] [ Correspondence: 1 | 2 ] [ Related articles and meeting reports: 1 | 2 | 3 | 4 | 5 ] [Authors: contact | web site ]

Beware that this article lacks competing financial interest declaration: Related reports 1 | 2 | 3

selected by Alexei Koudinov

Reduction in Levels of 24S-Hydroxycholesterol by Statin Treatment in Patients With Alzheimer Disease.
Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjohann D, Moore C, Svetlik D
Arch Neurology Apr 2003; 60(4): 510-5.
[PubMed] [ Abstract at Arch Neurol ] [Related articles: 1 | 2 | 3 | 4 ] [Authors contact]

selected by Ilya Reznik

Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability.
Hering H, Lin C-C, Sheng M.
J Neurosci. 15 April 2003 161(2): p. 621-30
[Abstract] [Related artiscles: 1 | 2 | 3 | 4 | 5 ] [Authors contact]
 

Keynote by Heike Hering: "Cholesterol/sphingolipid rafts are implicated in protein trafficking, cell signaling and in regulating the actin cytoskeleton. Depletion of cholesterol/sphingolipids in cultured hippocampal neurons leads to a gradual loss of synapses and spines, which is a central feature of neurodegenerative diseases caused by disordered cholesterol metabolism. Our data suggest that a major function of cholesterol and sphingolipids in neurons is to support lipid rafts, and that lipid rafts are important for normal synapse density and morphology."

selected by Temirbolat Berezov

CNS synaptogenesis promoted by glia-derived cholesterol.
Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A, Pfrieger FW.
Science. 9 Nov 2001 294: p. 1354-7.
[PubMed] [Related articles: 1 | 2 ] [Correspondence] [Authors contact]

selected by Temirbolat Berezov

Essential role for cholesterol in synaptic plasticity and neuronal degeneration.
Koudinov AR, Koudinova NV.
FASEB J. 2001 15(10): p. 1858-60
[PubMed] [FullText] [Synopsis] [Related articles: 1 | 2 | 3 | 4 | 5 | 6 ] [Authors: contact | web site ]
 

Keynote by Alexei R. Koudinov: "We experimentally modelled neuronal cholesterol metabolism disbalance by acute biochemical increase of the turnover of cholesterol in rat hippocampal slices. Such an experimental set up impairs the redistribution of cholesterol from one cell to another via lipoprotein transport. While increasing cholesterol removal or immediately thereafter, we evoked and recorded two brain waveforms, paired pulse facilitation (PPF) or long-term potentiation (LTP), which are indicative of neurotransmission and synaptic plasticity, respectively. We found that the lack of cholesterol supply to neurons impaired PPF and LTP. From additional immunofluorescent analysis of the slices, we demonstrated that cholesterol disbalance also caused neurodegeneration of hippocampal neural cell processes and the appearance of exessive tau phosphorylation in the mossy fibers. We also showed that LTP causes local (at the recording site) increase in lipids synthesis, indicating that synaptic plasticity depends on activity-dependent membrane lipid homeostasis modulation."

selected by Temirbolat Berezov

Isolation and Lipid Characterization of Cholesterol-Enriched Fractions in Cortical and Nuclear Human Lens Fibers.
Rujoi M, Jin J, Borchman D, Tang D, and Yappert MC.
Invest. Ophthalmol. Vis. Sci. April 2003 44(4): p. 1634-42
[PubMed] [Related article 1 ] [Authors contact]

selected by Alexei Koudinov

APP processing and synaptic function.
Kamenetz F, et al.
Neuron 27 March 2003; 37: p. 925-37
[Abstract/FullText] [Related articles 1 | 2 | 3 | ARF news: 1 | 2 ] [Authors contact]

Beware of the preliminary account for this article:

Activity dependent secretion of b-amyloid: roles of b -amyloid in synaptic transmission.
Kamenetz FR, Tomita T, Borchelt DR, Sisodia SS, Iwatsubo T, Malinow R.
Soc Neurosci Abstr 2000 26: p. 491
[Abstract]

selected by Alexei Koudinov

Membrane potential fluorescence: A rapid and highly sensitive assay for nicotinic receptor channel function.
Fitch RW, Xiao Y, Kellar KJ, and Daly JW.
Proc Nat Acad Sci USA. 25 March 2003; epub ahead of print: 10.1073/pnas.0630641100
[PubMed] [Authors contact]
 

Keynote by Richard W. Fitch: "Fluorescent measurement of membrane potential changes affords complementary information to that of currently used fluorescent calcium assays and is affected by changes in ionic balance due not only to calcium, but sodium and potassium, which are also passed by nicotinic receptors. In our hands this assay is more sensitive than the analogous calcium assay. This can be particularly important in cell lines with low receptor expression and/or receptor subtypes with low calcium permeability. In several cases we have investigated, calcium fluorescence changes were weak to absent, while membrane potential changes were robust. This method is useful both for pharmacological characterization of cell lines as well as for screening of compounds for nicotinic activity."

selected by Alexei Koudinov

Sphingolipid storage induces accumulation of intracellular cholesterol by stimulating SREBP-1 cleavage.
Puri V, Jefferson JR, Singh RD, Wheatley CL, Marks DL, and Pagano RE.
J Biol Chem. 25 March 2003; epub ahead of print: 10.1074/jbc.M300304200
[PubMed] [ Authors: contact | web site ]
 

Keynote by Richard E. Pagano: "This study examines the mechanism of cholesterol elevation in normal human skin fibroblasts induced by treatment with exogenous sphingolipids (SLs).  Elevated cholesterol was derived primarily from increased uptake of low density lipoproteins (LDL) which resulted from an up-regulation of LDL receptors (LDLR).  The unesterified cholesterol derived from this LDL accumulated with the exogenous SLs in late endosomes and lysosomes of the treated cells.  These results support a multi-step model in which excess SLs present in endocytic compartments serve as a “molecular trap” for LDL-derived cholesterol, leading to a reduction in cholesterol at the endoplasmic reticulum, induction of SREBP cleavage, and upregulation of LDLR.  Such a mechanism may be responsible for the high levels of intracellular cholesterol seen in SL storage disease cell types."

selected by Alexei Koudinov

The metabotropic glutamate receptor mGluR5 is endocytosed by a clathrin-independent pathway.
Fourgeaud L, Bessis A-S, Rossignol F, Pin J-P, Olivo-Marin J-C, and Hemar A.
J Biol Chem. 2003 278(14): p. 12222-12230
[PubMed] [Authors contact]

selected by Alexei Koudinov

Effects of dietary sphingomyelin on central nervous system myelination in developing rats.
Oshida K, Shimizu T, Takase M, Tamura Y, Shimizu T, and Yamashiro Y.
Pediatr. Res. 2003 53(4): p. 589-593
[PubMed] [Authors contact]

selected by Alexei Koudinov

Gene expression in two hepatic cell lines, cultured primary hepatocytes and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems.
Boess F. et al.
Toxicol. Sci. 25 March 2003; epub ahead of print: 10.1093/toxsci/kfg064.
[PubMed] [Authors contact]

selected by Alexei Koudinov

The formation of highly soluble oligomers of a-synuclein is regulated by fatty acids and enhanced in Parkinson's disease.
Sharon U, et al.
Neuron 20 Feb 2003; 37(4): p. 583-595
[PubMed] [Related articles 1 | 2 | 3 | 4 | 5 | ARF news: 1 ] [Authors contact]

Beware that this article lacks competing financial interest declaration: Related reports 1 | 2 | 3

Beware of earlier report on the same subject:

Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins.
Perrin RJ, Woods WS, Clayton DF, George JM
J Biol Chem 9 Nov 2001; 276(45): p. 41958-62
[PubMed] [Related article 1 ] [Authors contact]

selected by Alexei Koudinov

Cholesterol distribution in the golgi complex of astrocytes is differentially altered by fresh and aged amyloid b-peptide1-42.
Igbavboa U, et al.
J Biol Chem. 2003 Feb 12; epub ahead of print: 10.1074/jbc.M301150200
[PubMed] [Related article 1 | 2 | 3 | 4 ] [Authors contact]

selected by Alexei Koudinov

Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development.
Luque JM, Morante-Oria J, and Fairen A
Brain Res Dev Brain Res. 2003 Feb 16; 140(2): p. 195-203
[PubMed] [Related article 1 | 2 | 3 | 4 ] [Authors contact]

selected by Alexei Koudinov

Identification of phospholipid scramblase 1 as a novel interacting molecule with b-secretase (BACE).
Kametaka S, et al.
J Biol Chem. 2003 Feb 13; epub ahead of print: 10.1074/jbc.M208611200
[PubMed] [Authors contact]

selected by Alexei Koudinov

Dietary fats and the risk of incident Alzheimer Disease.
Clare Morris M, et al.
Arch Neurol. 2003 Feb 60: p. 194-200
[Abstract] [Related article 1 | 2 | 3 | 4 | 5 ] [Authors contact]

selected by Ilya Reznik

Lipid raft-dependent and -independent signaling through HLA-DR molecules.
Bouillon M, Fakhry YE, Girouard J, Khalil H, Thibodeau J, and Mourad W.
J Biol Chem. 2002 Dec 22; epub ahead of print: 10.1074/jbc.M211566200
[PubMed] [Related article 1 | 2 | 3 ] [Authors contact]
 

Keynote by Walid Mourad: "Lipid rafts are plasma membrane microdomains that are highly enriched in signaling molecules and that act as signal transduction platforms for many immune receptors. Although MHC class II molecules do not possess any known signaling motifs in their transmembrane domains, they act as signal transducers in addition to playing a critical role in antigen presentation. The relevance of these microdomains with regard to MHC class II-induced signal transduction pathways and APC function was poorly defined. Our results have permitted to show that localization of HLA-DR in these microdomains was crucial for rapid tyrosine phosphorylation of many substrates, especially of Lyn, and cell-cell adhesion, but not for ERK1/2 activation. Accordingly, some MHC class II-induced events require the presence of HLA-DR molecules in lipid rafts, whereas others do not."

selected by Alexei Koudinov

Fluorescence and multiphoton imaging resolve unique structural forms of sterol in membranes of living cells.
McIntosh AL, Gallegos AM, Atshaves BP, Storey SM, Kannoju D, and Schroeder F.
J Biol Chem. 21 Feb 2003 278(8): p. 6384-6403
[PubMed] [Related article 1 | 2 | 3 ] [Authors contact]

selected by Alexei Koudinov

22R-Hydroxycholesterol and 9-cis-retinoic acid induce ABCA1 transporter expression and cholesterol efflux in brain cells and decrease Abeta secretion.
Koldamova RP, et al.
J Biol Chem. 2003 Jan 22; epub ahead of print: 10.1074/jbc.M300044200
[PubMed] [Authors contact]
 

Keynote by Radosveta Koldamova: "Recent data suggest that high cholesterol level may contribute to the pathogenesis of Alzheimer's disease (AD). The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of peripheral cholesterol efflux and plasma HDL metabolism. In this study, we demonstrated that 22R-hydroxycholesterol and 9-cis-retinoic acid that are ligands for nuclear receptors LXR and RXR increased ABCA1 expression and apolipoprotein-specific cholesterol efflux in neurons and glia. Importantly, these ligands alone or in combination with apolipoprotein A-I caused a substantial reduction in the stability of APP C-terminal fragments and decreased amyloid b (Ab) production. These effects of LXR/RXR ligands may provide a novel strategy to decrease Ab secretion, and consequently reduce amyloid burden in the brain."

selected by Alexei Koudinov

The receptor-bound N-terminal ectodomain of the amyloid precursor protein is associated with membrane rafts.
Tikkanen R, Icking A, Beicht P, Waneck GL, and Volker H.
Biol Chem. December 2002 383(12): p. 1855-64
[PubMed] [Authors contact]

selected by Alexei Koudinov

Age-related deficits in long-term potentiation are insensitive to hydrogen peroxide: coincidence with enhanced autophosphorylation of Ca2+/calmodulin-dependent protein kinase II.
Watson JB, Khorasani H, Persson A, Huang KP, Huang FL, and O'Dell TJ.
J Neurosci Res. 1 November 2002 70(3): p. 298-308
[PubMed] [Related article 1 | 2 | 3 ] [Authors contact]

selected by Alexei Koudinov

Hydrogen peroxide modulation of synaptic plasticity
Kamsler A, and Segal M.
J Neurosci. 1 January 2003 23(1): p. 269-76
[PubMed] [Related article 1 | 2 ] [Authors contact]

selected by Alexei Koudinov

Apolipoprotein E e4 allele, AD pathology, and the clinical expression of Alzheimer's disease.
Bennett DA, et al.
Neurology 28 January 2003 60(2): p. 246-52
[Abstract] [Related article: 1 | 2 | 3 | ARF live discussion: 1 | 2 ] [Authors contact]

selected by Alexei Koudinov

APOE e4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy.
Tsuboi Y, Josephs KA, Cookson N, and Dickson DW.
Neurology 28 January 2003 60(2): p. 240-5
[PubMed] [Related article: 1 | 2 | ARF live discussion: 1 | 2 ] [Authors contact]
 

Keynote by Yoshio Tsuboi: "Progressive supranuclear palsy (PSP) and Alzheimer's disease (AD) are distinctive neurodegenerative disorders. PSP is characterized by motor abnormalities such as parkinsonism, severe postural instability and supranuclear gaze palsy. There may be a wider spectrum of clinical presentation in PSP including cortical abnormalities and memory dysfunction, sometimes due to overlapping AD pathology. We evaluated AD type pathology and APOE genotype in 173 pathologically proven cases of PSP. Only 26 cases had pathological aging and 14 cases had significant AD pathology, moreover, 19 of these 40 patients carried APOE e4 allele. Our study suggests that Alzheimer type pathology is an independent process unrelated to PSP in cases with both types of pathologies and that APOE e4 is a risk factor for Alzheimer type pathology in PSP."

selected by Alexei Koudinov

Cholesterol depletion by methyl-b-cyclodextrin blocks cholera toxin transport from endosomes to the Golgi apparatus in hippocampal neurons.
Shogomori H, Futerman AH
J. Neurochem. 2001 Sept; 78(5): p. 991-9
[PubMed] [Related article: 1 ] [Authors contact]

selected by Alexei Koudinov

Increased Brain b-Amyloid Load, Phosphorylated Tau, and Risk of Alzheimer Disease Associated With an Intronic CYP46 Polymorphism.
Papassotiropoulos A, et al.
Arch Neurol. 2003 Jan; 60: 113-23
[Abstract] [Commentary] [ARF Live Discussion] [Related NoLs: 1 | 2 | 3 | 4 | 5 | News: AP/ABC | AP/JN | NYT | Psych ] [ Patents ] [Authors contact]

Beware of earlier report on the same subject:

Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease.
Kölsch H, et al.
Mol Psychiatry 2002 Feb; 7(8): p. 899-202
[PubMed] [ARF news] [Authors contact]
 

Keynote by Heike Kölsch: "Elevated serum cholesterol and presence of at least one ApoE4 allele increase the risk of Alzheimer's disease (AD). We believe that brain cholesterol is mainly eliminated through the blood-brain-barrier after conversion to 24S-hydroxycholesterol by a cytochrome P450 enzyme, denoted CYP46. We screened the exons 2 and 3 of the CYP46 gene and detected two sequence variations, one of these influenced liquor concentrations of 24S-hydroxycholesterol/cholesterol in AD patients and the incidence of AD. It appears that brain cholesterol metabolism plays a more important role in the development of AD than previously assumed."

selected by Alexei Koudinov ; Psychiatry news item selected by Ilya Reznik

Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients.
Arvindakshan M, et al.
Biol Psychiatry 2003 Jan 1; 53(1): 56-64.
[PubMed] [Related articles: 1 | 2 ] [Authors contact]

selected by Ilya Reznik

Amyloidogenic processing of the Alzheimer b-amyloid precursor protein depends on lipid rafts.
Ehehalt R, Keller P, Haass C, Thiele C, and Simons K.
J Cell Biol. 2003 Jan 6; 160(1): 113-23
[PubMed] [Authors contact]
 

Keynote by Robert Ehehalt: "There is growing evidence that cholesterol is of particular importance in regulation a- and b-cleavage of APP. We show that lipid rafts, lateral assemblies of cholesterol and sphingolipids, are critically involved in APP processing. From our data we suggest that APP resides in two cellular pools within the membranes, one associated with lipid raft where Ab is generated and one outside rafts where APP is a-cleaved. This model of membrane compartimentation explains how APP could be processed in two mutually exclusive ways and how cholesterol - a key compound of lipid rafts - is participating in the regulation of these processes."

selected by Alexei Koudinov

Noteworthy 2002

Diet and risk of dementia: Does fat matter? The Rotterdam Study.
Engelhart MJ, et al.
Neurology 24 December 2002 59: p. 1915-21
[PubMed] [Related article: 1 ] [ARF news coverage] [Correspondence] [Authors contact]

Also see earlier report by the same group on the same subject using the Rotterdam study data:

Dietary fat intake and the risk of incident dementia in the Rotterdam Study.
Kalmijn S, et al.
Ann Neurology November 1997 42(5): p. 776-82
[PubMed] [Other Alzheimer's articles from the same group/Rotterdam study] [Authors contact]

selected by Alexei Koudinov

Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.
Karten B, Vance DE, Campenot RB, and Vance JE.
J Biol Chem. January 2003 278(6): 4168-75 (epub Nov 27, 2002 ahead of print: manuscript M205406200v1)
[PubMed] [Related articles: 1 | 2 ] [Authors contact]
 

Keynote by Jean E Vance: "A key characteristic of the neurodegenerative disorder Niemann-Pick Type C (NPC) disease is the accumulation of cholesterol in late endosomes due to a defect in intracellular trafficking of cholesterol. Using primary sympathetic neurons from a murine model of NPC disease we show that transport of endogenously-synthesized cholesterol into distal axons is reduced in NPC1-deficient neurons compared to wildtype neurons. Moreover, in contrast to wildtype neurons, NPC1-deficient neurons cannot efficiently utilize low density derived cholesterol for axonal growth when endogenous cholesterol synthesis is inhibited. Together with our previous observation that the cholesterol content of axons is reduced in NPC1-deficient neurons, and our finding that tNPC1 protein is present in both cell bodies and axons, these results implicate a key role for NPC1 in axonal cholesterol transport."

selected by Alexei Koudinov

An in vitro study of the effects of lovastatin on human fetal brain cells.
Pavlov OV, Bobryshev YuV, Balabanov YuV, and Ashwell K.
Neurotoxicol Teratol. 1995 17(1): p. 31-9
[PubMed] [Related articles: 1 | 2 | 3] [Authors contact]

selected by Alexei Koudinov

Structure of the LDL Receptor Extracellular Domain at Endosomal pH.
Rudenko G, et al.
Science. 2002 298(5602): p. 2353-8
[PubMed] [Authors contact]
 

Keynote by Gabby Rudenko: "The low density lipoprotein receptor (LDL-R) mediates cholesterol homeostasis in mammalian cells by removing LDL, a cholesterol carrying lipoprotein, from plasma circulation. It was known from biochemical studies that LDL-R binds LDL extracellularly at neutral pH, and then after being endocytosed, discharges its ligand in the endosomes at acidic pH. However the underlying molecular basis for ligand binding and release has been elusive. Using xray crystallography we now show that the LDL-R molecule a long modular molecule is found folded back on itself at endosomal pH, obscuring important ligand binding epitopes from solution. Our crystal structure suggests that at endosomal pH, the C-terminal part of the LDL-R molecule promotes ligand discharge by binding to its N-terminal part via ligand binding modules, thus displacing LDL."

selected by Alexei Koudinov

Resistance of human cerebrospinal fluid to in vitro oxidation is directly related to its amyloid-beta content.
Kontush A, Donarski N, and Beisiegel U.
Free Radic Res. 2001 35(5): p. 507-17
[PubMed] [Related articles: 1 | 2 | 3 | 4 ] [Authors contact]
 

Keynote by Anatol Kontush: "Amyloid-beta (Ab) peptide is normally secreted by neuronal cells and is present at low concentrations in cerebrospinal fluid (CSF) and plasma. The physiological role of Ab secretion, however, is understudied. We found that in 20 control subjects and 30 patients with Alzheimer's disease, the oxidative resistance of CSF samples is directly related to CSF levels of Ab 1-40, Ab 1-42, and ascorbate; and inversely related to the level of fatty acids. Consistent with our recent data (Kontush et al. Free Radic Biol Med. 30, 119, 2001), the findings suggest that, besides ascorbate, Ab is another major physiological antioxidant in the CSF."

selected by Temirbolat Berezov

Oxidized high-density lipoprotein induces neuron death.
Keller JN, Hanni KB, and Kindy MS.
Exp Neurol. 2002 161(2): p. 621-30
[PubMed] [Related articles: 1 | 2 | 3 ] [Authors contact]

selected by Temirbolat Berezov

Brain cholesterol pathology is the cause of Alzheimer's disease.
Koudinov AR, and Koudinova NV.
BMJ Clin Med Health Res. 17 November 2001 clinmed2001100005
[FullText] [Related articles: 1 | 2 | 3 ] [ARF Live Discussion] [Authors contact]
 

Keynote by Alexei Koudinov: "This is a companion report for our earlier contribution that provided evidence on the essential role for cholesterol in synaptic plasticity and neural degeneration (Koudinov & Koudinova FASEB J 2001 ; Science 2002). In this BMJ Clin Med article we explain why cholesterol homeostasis biological misregulation is the primary cause for several hallmarks of Alzheimer's disease not limited to brain amyloid. We also explain why Alzheimer's changes in neurochemistry of amyloid beta, tau, neuronal cytoskeleton, and oxidative stress reactions may represent physiological transitory mechanisms aiming to compensate impaired brain cholesterol dynamics and/or associated neurotransmission and synaptic plasticity failure (Also see SFN 2002 NoL sessions article). Contribution by others on the role for cholesterol in Alzheimer's disease is available at NoL symposium abstracts' article (Neurobiol Lipids 2002), and the Alzheimer Forum live discussion session (Neurobiol Lipids symposia).

selected by Temirbolat Berezov

Turnover of synaptic membranes: age-related changes and modulation by dietary restriction.
Ando S, Tanaka Y, Toyoda nee Ono Y, Kon K, and Kawashima S.
J. Neurosci. Res. 2002 70(3): p. 290-7
[Pub