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研究生:蔡弘毅
研究生(外文):Hung-I Tsai
論文名稱:膽固醇短缺加劇海馬迴星狀神經膠細胞因麩胺酸所誘發細胞死亡之機制探討
論文名稱(外文):Mechanistic study of cholesterol deficiency enhancing glutamate-induced cytotoxicity to hippocampal astrocytes
指導教授:周韻家
指導教授(外文):Yun-Chia Chou
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:71
中文關鍵詞:膽固醇膽固醇短缺神經膠細胞星狀神經膠細胞麩胺酸麩胺醯酸轉化酶
外文關鍵詞:cholesterolcholesterol deficiencygliaastrocyteglutamateglutamine synthetase
相關次數:
  • 被引用被引用:2
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  • 下載下載:18
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膽固醇對於哺乳動物的腦功能行使扮演著重要的角色。過去我們實驗室利用大白鼠的海馬迴星狀神經膠細胞培養作為實驗材料,發現當降低星狀神經膠細胞膽固醇含量, 所受到麩胺酸誘發的細胞死亡更為嚴重,但這個現象在海馬迴神經細胞上沒有發現。本論文的研究工作是要探討可能有哪些機制造成海馬迴星狀神經膠細胞膽固醇短缺時會加劇麩胺酸誘發的細胞死亡。
我發現到用lovastatin處理細胞時同時加入GGPP或者是FPP,可以減緩低海馬迴星狀神經膠細胞膽固醇含量加劇麩胺酸誘發的細胞死亡現象,GGPP和FPP是影響small GTPase protein作用的重要分子。此外在膽固醇短缺的海馬迴星狀神經膠細胞上可以發現到ERK1/2的磷酸化顯著上升,而ERK1/2是small GTPase protein的Ras訊號傳遞路徑下游分子,推測膽固醇短缺時海馬迴星狀神經膠細胞訊號傳遞會有所改變。此外我亦觀察到膽固醇短缺時海馬迴星狀神經膠細胞細胞形態明顯改變,同時actin結構有瓦解的現象,這樣的情況在海馬迴神經細胞上卻沒有見到,若在lovastatin處理海馬迴星狀神經膠細胞時同時加入GGPP或者是FPP,可減少細胞形態改變和actin結構的瓦解。當膽固醇短缺,對於海馬迴星狀神經膠細胞特有代謝麩胺酸的蛋白質麩胺醯酸轉化酶,我觀察到其表現量和活性有明顯下降,此外海馬迴星狀神經膠細胞膽固醇短缺時,可以觀察到細胞外有較多先以[3H]標記的天門冬胺酸 (麩胺酸的類似物)累積,推測膽固醇短缺時,海馬迴星狀神經膠細胞內麩胺醯酸轉化酶表現量和活性下降,使細胞內麩胺酸濃度上升,而較易溢出細胞外,造成膽固醇短缺的海馬迴星狀神經膠細胞外麩胺酸的累積量較高,可能因此加劇麩胺酸誘發的細胞死亡。
Cholesterol, a molecule critical for cellular function, is found in particular high concentration in the brain and has been implicated to synaptic plasticity and neuronal regeneration. We previously demonstrated that cholesterol deficiency exacerbated glutamate (Glu)-induced cytotoxicity to hippocampal glia, but not to neurons, in primary cultures. This study was undertaken to investigate the mechanism underlying the enhanced vulnerability of cholesterol-deficient astrocytes to Glu-induced cytotoxicity.
The detrimental effect of cholesterol depletion was partially abolished by both geranylgeranylpyrophosphate and farnesylpyrophosphate, molecules essential for prenyl modification of the small GTP-binding protein such as Ras. Cholesterol depletion by a combined treatment of lovastatin and β-cyclodextrin increased the phosphorylation of ERK 1/2, a downstream effector of Ras, in hippocampal astrocytes. In addition, we observed morphological changes, accompanied by disorganization of actin bundles in astrocytes of cholesterol deficiency. After cholesterol deprivation, there was a marked efflux of exogenous [3H] D-aspartate, a Glu analogue, from astrocytes upon stimulation by Glu. Cholesterol deprivation decreased the expression and the activity of glutamine synthetase, which converts Glu into glutamine.
We conclude that cholesterol deprivation affects signal transduction and impairs the integrity of cytoskeleton structure in astrocytes. Moreover, cholesterol depletion causes the buildup of a concentration gradient favoring Glu efflux from astrocytes. The elevated level of extracellular Glu thus accelerates the Glu-cytotoxicity to cholesterol deficient astrocytes.
Alberts A.W., Chen J., Kuron G., Hunt V., Huff J., Hoffman C., Rothrock J., Lopez M., Joshua H., Harris E., Patchett A., Monaghan R., Currie S., Stapley E., Albers-Schonberg G., Hensens O., Hirshfield J., Hoogsteen K., Liesch J., and Springer J. (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc. Natl. Acad. Sci. U. S. A. 77:3957-3961.
Andersson M., Aberg F., Teclebrhan H., Edlund C., and Appelkvist E.L. (1995) Age-dependent modifications in the metabolism of mevalonate pathway lipids in rat brain. Mech. Ageing Dev. 85:1-14.
Arriagada P.V., Marzloff K., and Hyman B.T. (1992) Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer''s disease. Neurology 42:1681-1688.
Bakhit, C., Armanini, M., Bennett, G.L., Wong, W.l.T., Hansen, S.E., and Taylor, R. (1991) Increase in glia-derived nerve growth factor following destruction of hippocampal neurons. Brain Res. 560:76-83.
Bastiaanse E. M., Hold K. M., and Van der Laarse A. (1997) The effect of membrane cholesterol content on ion transport processes in plasma membranes. Cardiovasc. Res. 33:272–283.
Baroto D. M., Mellado W., and Shelanski M. L. (1992) Astrocyte process growth induction by actin breakdown. J. Cell Bio. 117:357-367.
Baulieu E. E., Robel P. and Schumacher M. (2001) Neurosteroids:beginning of the story. Int. Rev. Neurobiol. 46:1–32.
Beffert U., Aumont N., Dea D., Suzanne LC., Davignon J., and Poirier J. (1999) Apolipoprotein E isoform-specific reduction of extracellular amyloid in neuronal cultures. Mol. Brain Res. 68:181–185.
Boston P.F., Dursun S.M., and Reveley M.A. (1996) Cholesterol and mental disorder. Br. J. Psychiatry 169:682-689.
Bouvier M., Szatkowski M., Amato A., and Attwell D. (1992) The glial cell glutamate uptake carrier countertransports pH-changing anions. Nature 360:471-474.
Bradke F., Dotti C.G., (1999) The role of local actin instability in
axon formation. Science 283:1931–1934.
Brown M.S., and Goldstein J.L. (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34-47.
Buttini M., Orth M., Bellosta S., Akeefe H., Pitas R.E., Wyss-Coray T., Mucke L., and Mahley R.W. (1999) Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice : isoform-specific effects on neurodegeneration. J. Neurosci. 19:4867-4880.
Choi D.W. (1988) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 11:465-469.
Chou Y. C., Lin S. B., Tsai L. H., Tsai H. I., and Lin C. M. (2003) Cholesterol deficiency increases the vulnerability of hippocampal glia in primary culture to glutamate-induced excitotoxicity. Neurochem. Int. 43:197–209.
Crook R., Ellis R., Shanks M., Thal L.J., Perez-Tur J., Baker M., Hutton M., Haltia T., Hardy J., and Galasko D. (1997) Early-onset Alzheimer''s disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation. Ann. Neurol. 42:124-128.
Csernansky J.G., Bardgett M.E., Sheline Y.I., Morris J.C., and Olney J.W. (1996) CSF excitatory amino acids and severity of illness in Alzheimer''s disease. Neurology 46:1715-1720.
de Vellis J. (1993) Supporting cells:Central and Peripheral. In: Gorio A. ed. Neuroregeneration. New York: Raven Press. Ltd. pp.61-75.
Dietschy J.M., and Turley S.D. (2001) Cholesterol metabolism in the brain. Curr. Opin. Lipidol. 12:105-112.
Dringen R., Gutterer J.M., Hirrlinger J. (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species, Eur. J. Biochem. 267:4912–4916.
Edmond J., Korsak R.A., Morrow J.W., Torok-Both G., and Catlin D.H. (1991) Dietary cholesterol and the origin of cholesterol in the brain of developing rats. J. Nutr. 121:1323-1330.
Fassbender K., Simons M., Bergmann C., Stroick M., Lütjohann D., Keller P., Runz H., Kühl S., Bertsch T., Bergmann K.V., Hennerici M., Beyreuther K., and Hartmann T. (2001) Simvastatin strongly reduces levels of Alzheimer’s disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 98:5856–5861.
Ganong, W.F. (1995) Review of medical physiology. 17th ed., Appleton & Lange, London, pp.277-280.
Gimpl G., Burger K., and Fahrenholz F. (1997) Cholesterol as modulator of receptor function. Biochem. 36:10959-10974.
Ghosh P.M., Nandini G., Moyer M.L., Mott G.E., Thomas C.A., Foster B.A., Greenberg N.M., and Kreisberg J.I. (1999) Role of RhoA activation in the growth and morphology of murine prostate tumor cell line. Oncogene 18:4120-4130.
Goldberg M.P., and Choi D.W. (1993) Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J. Neurosci. 13:3510-3524.
Goldstein J.L., Kita T., and Brown M.S. (1983) Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N. Engl. J. Med. 309:288-396.
Gorovit R., Avidan N., Avisar N., Shaked I., and Vardimon L. (1997) Glutamine synthetase protects against neuronal degeneration in injured retinal tissue. Proc. Natl. Acad. Sci. U. S.A. 94:7024–7029.
Gregg R.E., Zech L.A., Schaefer E.J., Stark D., Wilson D., and Brewer H.B. Jr. (1986) Abnormal in vivo metabolism of apolipoprotein E4 in humans. J. Clin. Invest. 78:815-821.
Guillaume D., Bertrand P., Dea D., Davignon J., and Poirier J. (1996) Apolipoprotein E and low-density lipoprotein binding and internalization in primary cultures of rat astrocytes: isoform-specific alterations. J. Neurochem. 66:2410-2418.
Hamanaka H., Katoh-Fukui Y., Suzuki K., Kobayashi M., Suzuki R., Motegi Y., Nakahara Y., Takeshita A., Kawai M., Ishiguro K., Yokoyama M., and Fujita S.C. (2000) Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice. Hum. Mol. Genet. 9:353-361.
Igbavboa U., Avdulov N.A., Chochina S.V., and Wood W.G. (1997) Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins. J. Neurochem. 69:1661-1667.
Ishimaru H., Ishikawa K., Haga S., Shoji M., Ohe T., Haga C., Sasaki A., Takashashi A., and Maruyama Y. (1996) Accumulation of apolipoprotein E and beta-amyloid-like protein in a trace of the hippocampal CA1 pyramidal cell layer after ischaemic delayed neuronal death. Neuroreport 7:3063-3067.
Jabaudon D., Shimamoto K., Yasuda-Kamatani Y., Scanziani M., Gähwiler B. H., and Gerber U. (1999) Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin. Proc. Natl. Acad. Sci. U.S.A. 96:8733-8738.
Jiang C., Xia Y., and Haddad G.G. (1992) Role of ATP-sensitive K+ channels during anoxia: major differences between rat (newborn and adult) and turtle neurons. J. Physiol. 448:599-662.
Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. and Drachman, D. A. (2000) Statin and the risk of dementia.Lancet 356:1627–1631.
Jimenez-Jimenez F.J., Molina J.A., Gomez P., Vargas C., de Bustos F., Benito-Leon J., Tallon-Barranco A., Orit-Pareja M., Gasalla T., and Arenas J. (1998) Neurotransmitter amino acids in cerebrospinal fluid of patients with Alzheimer''s disease. J. Neural. Transm. 105:269-277.
Kanai Y, Trotti D, Nussberger S, Hediger MA. (1997) The high affinity glutamate transporter family. In: Neurotransmitter transporters: structure,function, and regulation (Reith MEA, ed), pp.171–213.
Kilsdonk E.P., Yancey P.G., Stoudt G.W., Bangerter F.W., Johnson W.J., Phillips M.C., and Rothblat G.H. (1995) Cellular cholesterol efflux mediated by cyclodextrin. J. Biol. Chem. 270:17250-17256.
Knopfel T., Lukic S., Leonard T., Flor P.J., Kuhn R., and Gasparini F. (1995) Pharmacological characterization of MCCG and MAP4 at the mGluR1b, mGluR2 and mGluR4a human metabotropic glutamate receptor subtypes. Neuropharmacology 34:1099-1102.
Kojro E., Gimpl G., Lammich S., März W., and Fahrenholz F. (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the a-secretase ADAM 10. Proc. Natl. Acad. Sci. U. S. A. 98:5815-5820.
Kosenko E., Llansola M., Montoliu C., Monfort P., Rodrigo R., Hernandez-Viadel M., Erceg S., Sánchez-Perez A. M., and Felipo V. (2003) Glutamine synthetase activity and glutamine content in brain : modulation by NMDA receptors and nitric oxide. Neurochem. Int. 43 :493–499.
Kranenburg O., Verlaan I. and Moolenaar W. H. (2001) Regulating c-Ras function: cholesterol depletion affects caveolin association, GTP loading, and signaling. Curr. Biol. 11:1880-1884.
Kwik J., Boyle S., Fooksman D., Margolis L., Sheetz M P., and Edidin M. (2003) Membrane cholesterol, lateral mobility, andthe phosphatidylinositol 4,5-bisphosphatedependent organization of cell actin. Proc. Natl. Acad. Sci. U. S. A. 100:13964-13969.
LaFerla F.M., Troncoso J.C., Strickland D.K., Kawas C.H., and Jay G. (1997) Neuronal cell death in Alzheimer''s disease correlates with apoE uptake and intracellular Abeta stabilization. J. Clin. Invest. 100:310-320.
Laurence H. A., Diane-Berangere R., Andre N., and Lydia K. G. (2002) Importance of astrocytic inactivation of synaptically released glutamate for cell survival in the central bervous system-are astrocytes vulnerable to low intracellular glutamate concentrations. J. Physio. (Paris) 96:317-322.
Lehre K.P., and Danbolt N.C. (1998) The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J Neurosci 18:8751–8757.
Lipton S.A., and Rosenberg P.A. (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med. 330:613-622.
Liuzzi, F.J., and Lasek, R.J. (1987) Astrocyte block axonal regeneration in mammals by  activating the physiological stop pathway. Science 237:642-645.
Lutjohann D., Papassotiropoulos A., Bjorkhem I., Locatelli S., Bagli M., Oehring R.D., Schlegel U., Jessen F., Rao M.L., von Bergmann K., and Heun R. (2000) Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J. Lipid Res. 41:195-198.
Mahley R. W., and Rall S. C. Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu. Rev. Genom. Hum. Genet. 1:507–537.
Mann R. K., and Beachy P. A. (2000) Cholesterol modification of proteins. Biochim. Biophys. Acta 1529:188–202.
Masliah E., Mallory M., Veinbergs I., Miller A., and Samuel W. (1996) Alterations in apolipoprotein E expression during aging and neurodegeneration. Prog. Neurobiol. 50:493-503.
Masliah E., Terry R.D., Mallory M., Alford M., and Hansen L.A. (1990) Diffuse plaques do not accentuate synapse loss in Alzheimer''s disease. Am. J. Pathol. 137:1293-1297.
Mason R.P., Shoemaker W.J., ShajenKo L., Chamber T.E., and Herbette L.G. (1992) Evidence for changes in the Alzheimer''s disease brain cortical membrane structure mediated by cholesterol. Neurobiol. Aging 13:413-419.
Mattson M.P., Barger S.W., Cheng B., Lieberburg I., Smith-Swintosky V.L., and Rydel R.E. (1993) beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer''s disease. Trends Neurosci. 16:409-14.
Mauch D.H., Nagler K., Schumacher S., Goritz C., Muller E.C., Otto A.,and Pfrieger1 F.W. (2001) CNS Synaptogenesis Promoted by Glia-Derived Cholesterol. Science 294:1354-1357
Meldrum B., and Garthwaite J. (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci. 11:379-387.
Mellon S. H. and Griffin L. D. (2002) Neurosteroids: biochemistry and clinical significance. Trends Endocrinol. Metab. 13:35–43.
Messmer-Joudrier S., Sagot Y., Mattenberger L., James R.W., and Kato A.C. (1996) Injury-induced synthesis and release of apolipoprotein E and clusterin from rat neural cells. Eur. J. Neurosci. 8:2652-2661.
Michikawa M., and Yanagisawa K. (1998) Apolipoprotein E4 induces neuronal cell death under conditions of suppressed de novo cholesterol synthesis. J. Neurosci. Res. 54:58-67.
Michikawa M., Fan O.W. Isobe I., and Yanagisawa K. (2000) Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes and neurons in culture. J. Neurochem. 74:1008-1016.
Morgan R.E., Palinkas L.A., Barrett Connor E.L., and Wingard D.L. (1993) Plasma cholesterol and depressive symptoms in older man. Lancet 341:75-79
Mullan M., and Crawford F. (1993) Genetic and molecular advances in Alzheimer''s disease. Trends Neurosci. 16:398-403.
Nakanishi S. (1992) Molecular diversity of glutamate receptors and implications for brain function. Science 258:597-603.
Nathan B.P., Bellosta S., Sanan D.A., Weisgraber K.H., Mahley R.W., and Pitas R.E. (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 264:850-852.
Nicholls D., and Attwell D. (1990) The release and uptake of excitatory amino acids. Trends Pharmacol. Sci. 11:462-468.
Niggli V., Meszaros A. V., Oppliger C., and Tornay S. (2004) Impact of cholesterol depletion on shape changes, actin reorganization,and signal transduction in neutrophil-like HL-60 cells. Exp. Cell Res. 296:358-368.
Nobes C.D., and Hall A. (1995) Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress .bres, lamellipodia and .lopodia. Cell 81:53–62.
Olney J.W., Wozniak D.F., and Farber N.B. (1997) Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. Arch. Neurol. 54:1234-1240.
Pavlov O.V., Bobryshev Y.V., Balabanov Y.V., and Ashwell K. (1995) An in vitro study of the effects of lovastatin on human fetal brain cell. Neurotoxicol. Teratol. 17:31-39.
Peghini P., Janzen J., and Stoffel W. (1997) Glutamate transporter EAAC-1- deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. EMBO J. 16:3822–3832.
Pfrieger F.W. (2003) Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? Bioessays 25:72–78.
Pin J.P., and Duvoisin R. (1995) The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34:1-26.
Pitha J., Irie T., Sklar P.B., and Nye J.S. (1988) Drug solubilizers to aid pharmacologists: amorphous cyclodextrin derivatives. Life Sci. 43:493-502.
Poirier J., Baccichet A., Dea D., and Gauthier S. (1993) Cholesterol synthesis and lipoprotein reuptake during synaptic remodeling in hippocampus in adult rats. Neurosci. 55:88-90.
Rando, R.R. (1996) Chemical biology of protein isoprenylation/methylation. Biochim. Biophys. Acta. 1300:5-16.
Rhoades R., and Pflanzer, R. (1996) Human Physiology, 3rd ed. Saunders College Publishing. pp. 231-244.
Richter C., Park J.W., and Ames B.N. (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci. U.S.A. 85:6465-6467.
Ridley A., and Hall A. (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibres in response to growth factors. Cell 70:389–399.
Ridley A.J., Paterson H.F., Johnston C.L., Diekmann D., and Hall A. (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401–410.
Robinson S. R. (2001) Changes in the Cellular Distribution of Glutamine Synthetase in Alzheimer’s disease. J Neurosci. Res. 66:972–980.
Rocca W.A., Hofman A., Brayne C., Breteler M.M., Clarke M., Copeland J.R., Dartigues J.F., Engedal K., Hagnell O., and Heeren T.J. (1991) Frequency and distribution of Alzheimer''s disease in Europe: a collaborative study of 1980-1990 prevalence findings. Ann. Neurol. 30:381-390.
Rossi D.J., Oshima T., and Attwell D. (2000) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403:316-321.
Rothman S.M., and Olney J.W. (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann. Neurol. 19:105-111.
Rothstein J.D., Martin L., Levey A.I., Dykes-Hoberg M., Jin L., Wu D., Nash N., and Kuncl R.W. (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713–725.
Saunders A.M., Strittmatter W.J., Schmechel D., George-Hyslop P.H.,Pericak-Vance M.A., Joo S.H., Rosi B.L., Gusella J.F., Crapper-MacLachlan D.R., Alberts M.J., Hulette C., Crain B., Goldgaber D., and Roses A.D. (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer''s disease. Neurology 43:1467-1472.
Schaeffer H.J., and Weber M.J. (1999) Mitogen-activated protein kinases:specific messages from ubiquitous messengers. Mol. Cell Biol. 19:2435-2444.
Selkoe D.J. (1991) The molecular pathology of Alzheimer''s disease. Neuron 6:487-498.
Selkoe D.J. (1993) Physiological production of the beta-amyloid protein and the mechanism of Alzheimer''s disease. Trends Neurosci. 16:403-409.
Selkoe D.J. (2000) The genetics and molecular pathology of Alzheimer''s disease: roles of amyloid and the presenilins. Neurol. Clin. 18:903-922.
Simons M., Keller P., Strooper B.D., Beyreuther K., Dotti C.G., and Simon K. (1998) Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc. Natl. Acda. Sci. U.S.A. 95:6460-6464.
Smith C.D., Carney J.M., Starke-Reed P.E., Oliver C.N., Stadtman E.R., Floyd R.A., and Markesbery W.R. (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 88:10540-10543.
Snipes G.J., McGuire C.B., Norden J.J., and Freeman J.A. (1986) Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. Proc. Natl. Acad. Sci. U.S.A. 83:1130-1134.
Soberderg M., Edlund C., Kristensson K., and Dallner G. (1990) Lipid compositions of different regions of the human brain during aging. J. Neurochem. 54:415-423.
Sochocka E., Juurlink B.H., Code W.E., Hertz V., Peng L., and Hertz L. (1994) Cell death in primary cultures of mouse neurons and astrocytes during exposure to and ''recovery'' from hypoxia, substrate deprivation and simulated ischemia. Brain Res. 638:21-28.
Sparks, D. L., S. W. Scheff, J. C. Hunsaker, H. Liu, T. Landers, and D. R. Gross. (1994) Induction of Alzheimer-like β-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp. Neurol. 126: 88–94.
Spector A. A. and Yorek M. A. (1985) Membrane lipid composition and cellular function. J. Lipid Res. 26:1015–1035.
Stoffel-Wagner B. (2001) Neurosteroid metabolism in the humanbrain. Eur. J. Endocrinol. 145:669–679.
Swanson L. W., Simmons D. M., Hofmann S. L., Goldstein J. L. and Brown M. S. (1988) Localization of mRNA for low density lipoprotein receptor and a cholesterol synthetic enzyme in rabbit nervous system by in situ hybridization. Proc.Natl. Acad. Sci. U.S.A. 85: 9821–9825.
Svennerholm L., and Gottfries C.G. (1994) Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J. Neurochem. 62:1039-1047.
Strittmatter W. J. and Bova H. C. (2002) Molecular biology of apolipoprotein E. Curr. Opin. Lipidol. 13:119–123.
Tabas I. (2002) Cholesterol in health and disease. J. Clin. Invest. 110: 583–590.
Takai Y., Sasaki T., and Matozaki T. (2001) Small GTP-binding proteins. Physiol. Rev. 81:153–208.
Takami K. (2002) Neuroprotective Effects of the Green Tea Components Theanine and Catechins. Biol. Pharm. Bull. 25:1513-1518.
Tanaka K. (2000) Functions of glutamate transporters in the brain. Neurosci Res 37:15–19.
Tsutsui K., Ukena K., Usui M., Sakamoto H. and Takase M.(2000) Novel brain function: biosynthesis and actions of neurosteroidsin neurons. Neurosci. Res. 36: 261–273.
Turski L., Bressler K., Rettig K.J., Loschmann P.A., and Wachtel H. (1991) Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 349:414-418.
Urano S., Sato Y., Otonari T., Makabe S., Suzuki S., Ogata M., and Endo T. (1998) Aging and oxidative stress in neurodegeneration. Biofactors 7:103-112.
Wahrle, S., Das P., Nyborg A.C., McLendon C., Shoji M., Kawarabayashi T., Younkin L. H., Younkin S. G., and Golde T. E. (2002) Cholesterol-dependent γ-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol. Dis. 9:11–23.
Wolozin, B., Kellman W., Ruosseau P., Celesia G.G. and Siegel G. (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 57: 1439–1443.
Wong T.K., and Lennarz W.J. (1982) Biosynthesis of dolicol and cholesterol during embryonic development of the chicken. Biochem. Biophys. Acta. 710:32-38.
Yeagle P.L. (1985) Cholesterol and the cell membrane. Biochim. Biophys. Acta 822:267–287.
Yeagle P.L. (1991) Modulation of membrane function by cholesterol. Biochem. 73:1303-1310.
Zannis V.I., and Breslow J.L. (1981) Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification. Biochem. 20:1033-1041.
Zerial M., and McBride H. (2001) Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2:107–117.
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