PS Dependent APP Cleavage Regulates Glucosylceramide Synthase and is Affected in Alzheimer's Disease

Cellular Physiology and Biochemistry

Volumn 34, Issue 1, 2014, Pages 92-110

  Grimm, Marcus O W ^a,b   Hundsdörfer, Benjamin ^a   Grösgen, Sven ^a   Mett, Janine ^a   Zimmer, Valerie C ^a   Stahlmann, Christoph P ^a   Haupenthal, Viola J ^a   Rothhaar, Tatjana L ^a   Lehmann, Johannes ^a   Pätzold, Andreas ^c   Zinser, Eva G ^a   Tanila, Heikki ^d   Shen, Jie ^e   Müller, Ulrike ^c   Grimm, Heike S ^a   Hartmann, Tobias ^a,b  

^a SAARLAND UNIVERSITY   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d UNIVERSITY OF EASTERN FINLAND   (Finland)

^e HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Gangliosides; Glucosylceramide synthase; Presenilin

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CERAMIDE GLUCOSYLTRANSFERASE; GAMMA SECRETASE INHIBITOR; GANGLIOSIDE; GLUCOSYLCERAMIDE; PRESENILIN; APLP2 PROTEIN, MOUSE; GLUCOSYLTRANSFERASE; SECRETASE; URIDINE DIPHOSPHATE GLUCOSE;

ADULT; AGED; ALZHEIMER DISEASE; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVITY; ENZYME REGULATION; FEMALE; GENE EXPRESSION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MALE; MASS SPECTROMETRY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; REAL TIME POLYMERASE CHAIN REACTION; SYNTHESIS; THIN LAYER CHROMATOGRAPHY; TRANSGENIC MOUSE; WESTERN BLOTTING; ANIMAL; BRAIN; CELL LINE; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; DEFICIENCY; ENZYMOLOGY; GENETIC TRANSFECTION; GENETICS; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY; ADOLESCENT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; HUMAN TISSUE; PROTEIN DEFICIENCY; VERY ELDERLY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BRAIN; CELL LINE; CERCOPITHECUS AETHIOPS; COS CELLS; FEMALE; GANGLIOSIDES; GLUCOSYLTRANSFERASES; HUMANS; MALE; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; PRESENILINS; TRANSFECTION;

MUS MUSCULUS;

EID: 84903948746     PISSN: 10158987     EISSN: 14219778     Source Type: Journal    
DOI: 10.1159/000362987     Document Type: Article

References (90)

1. AD international, World Alzheimer Report: Alzheimer's Disease International Consortium, 2009.
2. Selkoe DJ: Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nat Cell Biol 2004;6:1054-1061. (Pubitemid 39468006)
3. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K: Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 1985;82:4245-4249. (Pubitemid 15053619)
4. Zhang H, Ma Q, Zhang YW, Xu H: Proteolytic processing of Alzheimer's beta-amyloid precursor protein. J Neurochem 2012;120:S9-21.
5. Pardossi-Piquard R, Checler F: The physiology of the beta-amyloid precursor protein intracellular domain aicd. J Neurochem 2012;120:S109-124.
6. Steiner H, Fluhrer R, Haass C: Intramembrane proteolysis by gamma-secretase. J Biol Chem 2008;283:29627-29631.
7. St George-Hyslop PH, Petit A: Molecular biology and genetics of Alzheimer's disease. C R Biol 2005;328:119-130. (Pubitemid 40247057)
8. Brown MS, Ye J, Rawson RB, Goldstein JL: Regulated intramembrane proteolysis: A control mechanism conserved from bacteria to humans. Cell 2000;100:391-398.
9. Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin SG, Golde TE: Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol Dis 2002;9:11-23. (Pubitemid 34174561)
10. Grimm MO, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T: Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol 2005;7:1118-1123.
11. Grimm MO, Zinser EG, Grösgen S, Hundsdorfer B, Rothhaar TL, Burg VK, Kaestner L, Bayer TA, Lipp P, Muller U, Grimm HS, Hartmann T: Amyloid precursor protein (app) mediated regulation of ganglioside homeostasis linking Alzheimer's disease pathology with ganglioside metabolism. PLoS One 2012;7:e34095.
12. Grimm MO, Kuchenbecker J, Grösgen S, Burg VK, Hundsdorfer B, Rothhaar TL, Friess P, de Wilde MC, Broersen LM, Penke B, Peter M, Vigh L, Grimm HS, Hartmann T: Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms. J Biol Chem 2011;286:14028-14039.
13. Grimm MO, Rothhaar TL, Grösgen S, Burg VK, Hundsdorfer B, Haupenthal VJ, Friess P, Kins S, Grimm HS, Hartmann T: Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (app). J Nutr Biochem 2012;23:1214-1223.
14. Grimm MO, Grimm HS, Tomic I, Beyreuther K, Hartmann T, Bergmann C: Independent inhibition of Alzheimer disease beta-and gamma-secretase cleavage by lowered cholesterol levels. J Biol Chem 2008;283:11302-11311.
15. Grimm MO, Zimmer VC, Lehmann J, Grimm HS, Hartmann T: The impact of cholesterol, dha, and sphingolipids on Alzheimer's disease. BioMed Res Int 2013;2013:814390.
16. Fishman PH, Brady RO: Biosynthesis and function of gangliosides. Science 1976;194:906-915.
17. Landa CA, Maccioni HJ, Arce A, Caputto R: The biosynthesis of brain gangliosides. Separation of membranes with different ratios of ganglioside sialylating activity to gangliosides. Biochem J 1977;168:325-332. (Pubitemid 8246916)
18. Degroote S, Wolthoorn J, van Meer G: The cell biology of glycosphingolipids. Semin Cell Dev Biol 2004;15:375-387. (Pubitemid 38781900)
19. Svennerholm L, Bostrom K, Jungbjer B, Olsson L: Membrane lipids of adult human brain: Lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem 1994;63:1802-1811. (Pubitemid 24326224)
20. Kracun I, Rosner H, Drnovsek V, Heffer-Lauc M, Cosovic C, Lauc G: Human brain gangliosides in development, aging and disease. Int J Dev Biol 1991;35:289-295.
21. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP: Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci U S A 2004;101:2070-2075. (Pubitemid 38229016)
22. Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE, Small SA, Wenk MR, Shui G, Di Paolo G: Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem 2012;287:2678-2688.
23. Gottfries CG, Karlsson I, Svennerholm L: Membrane components separate early-onset Alzheimer's disease from senile dementia of the Alzheimer type. International psychogeriatrics / IPA 1996;8:365-372. (Pubitemid 27067586)
24. Molander-Melin M, Blennow K, Bogdanovic N, Dellheden B, Mansson JE, Fredman P: Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides gm1 and gm2 and loss of cholesterol in detergent-resistant membrane domains. J Neurochem 2005;92:171-182. (Pubitemid 40193519)
25. Zha Q, Ruan Y, Hartmann T, Beyreuther K, Zhang D: Gm1 ganglioside regulates the proteolysis of amyloid precursor protein. Mol Psychiatry 2004;9:946-952. (Pubitemid 39381958)
26. Yanagisawa K, Odaka A, Suzuki N, Ihara Y: Gm1 ganglioside-bound amyloid beta-protein (a beta): A possible form of preamyloid in Alzheimer's disease. Nat Med 1995;1:1062-1066.
27. Krivit W, Desnick RJ, Lee J, Moller J, Wright F, Sweeley CC, Snyder PD Jr, Sharp HL: Generalized accumulation of neutral glycosphingolipids with gm2 ganglioside accumulation in the brain. Sandhoff's disease (variant of tay-sachs disease). Am J Med 1972;52:763-770.
28. Tamboli IY, Hampel H, Tien NT, Tolksdorf K, Breiden B, Mathews PM, Saftig P, Sandhoff K, Walter J: Sphingolipid storage affects autophagic metabolism of the amyloid precursor protein and promotes abeta generation. J Neurosci 2011;31:1837-1849.
29. Keilani S, Lun Y, Stevens AC, Williams HN, Sjoberg ER, Khanna R, Valenzano KJ, Checler F, Buxbaum JD, Yanagisawa K, Lockhart DJ, Wustman BA, Gandy S: Lysosomal dysfunction in a mouse model of sandhoff disease leads to accumulation of ganglioside-bound amyloid-beta peptide. J Neurosci 2012;32:5223-5236.
30. Robinson A, Grosgen S, Mett J, Zimmer VC, Haupenthal VJ, Hundsdorfer B, C PS, Slobodskoy Y, Muller UC, Hartmann T, Stein R, Grimm MO: Upregulation of pgc-1alpha expression by Alzheimer's disease-associated pathway: Presenilin 1/amyloid precursor protein (app)/intracellular domain of app. Aging cell 2013;13:263-272.
31. Grimm MO, Grösgen S, Rothhaar TL, Burg VK, Hundsdorfer B, Haupenthal VJ, Friess P, Muller U, Fassbender K, Riemenschneider M, Grimm HS, Hartmann T: Intracellular app domain regulates serine-palmitoyl-coa transferase expression and is affected in Alzheimer's disease. Int J Alzheimers Dis 2011;2011:695413.
32. Grimm MO, Kuchenbecker J, Rothhaar TL, Grösgen S, Hundsdorfer B, Burg VK, Friess P, Muller U, Grimm HS, Riemenschneider M, Hartmann T: Plasmalogen synthesis is regulated via alkyl-dihydroxyacetonephosphate-synthase by amyloid precursor protein processing and is affected in Alzheimer's disease. J Neurochem 2011;116:916-925.
33. Ring S, Weyer SW, Kilian SB, Waldron E, Pietrzik CU, Filippov MA, Herms J, Buchholz C, Eckman CB, Korte M, Wolfer DP, Muller UC: The secreted beta-amyloid precursor protein ectodomain apps alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of app-deficient mice. J Neurosci 2007;27:7817-7826. (Pubitemid 47093823)
34. Saura CA, Chen G, Malkani S, Choi SY, Takahashi RH, Zhang D, Gouras GK, Kirkwood A, Morris RG, Shen J: Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J Neurosci 2005;25:6755-6764. (Pubitemid 41023143)
35. Casas C, Sergeant N, Itier JM, Blanchard V, Wirths O, van der Kolk N, Vingtdeux V, van de Steeg E, Ret G, Canton T, Drobecq H, Clark A, Bonici B, Delacourte A, Benavides J, Schmitz C, Tremp G, Bayer TA, Benoit P, Pradier L: Massive ca1/2 neuronal loss with intraneuronal and n-terminal truncated abeta42 accumulation in a novel Alzheimer transgenic model. Am J Pathol 2004;165:1289-1300. (Pubitemid 39297734)
36. Rothhaar TL, Grösgen S, Haupenthal VJ, Burg VK, Hundsdorfer B, Mett J, Riemenschneider M, Grimm HS, Hartmann T, Grimm MO: Plasmalogens inhibit app processing by directly affecting gamma-secretase activity in Alzheimer's disease. ScientificWorldJournal 2012;2012:141240.
37. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method. Methods 2001;25:402-408. (Pubitemid 34164012)
38. Grimm HS, Beher D, Lichtenthaler SF, Shearman MS, Beyreuther K, Hartmann T: Gamma-secretase cleavage site specificity differs for intracellular and secretory amyloid beta. J Biol Chem 2003;278:13077-13085. (Pubitemid 36805601)
39. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC: Measurement of protein using bicinchoninic acid. Anal Biochem 1985;150:76-85. (Pubitemid 16258399)
40. Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959;37:911-917.
41. Matsuo N, Nomura T, Imokawa G: A rapid and simple assay method for udp-glucose:Ceramide glucosyltransferase. Biochim Biophys Acta 1992;1116:97-103.
42. Jeckel D, Karrenbauer A, Burger KN, van Meer G, Wieland F: Glucosylceramide is synthesized at the cytosolic surface of various golgi subfractions. J Cell Biol 1992;117:259-267.
43. Bourteele S, Hausser A, Doppler H, Horn-Muller J, Ropke C, Schwarzmann G, Pfizenmaier K, Muller G: Tumor necrosis factor induces ceramide oscillations and negatively controls sphingolipid synthases by caspases in apoptotic kym-1 cells. J Biol Chem 1998;273:31245-31251. (Pubitemid 28533140)
44. Whitfield P, Johnson AW, Dunn KA, Delauche AJ, Winchester BG, Franklin RJ: Gm1-gangliosidosis in a cross-bred dog confirmed by detection of gm1-ganglioside using electrospray ionisation-tandem mass spectrometry. Acta Neuropathol (Berl) 2000;100:409-414. (Pubitemid 30497011)
45. Christie WW: Analysis of phospholipids and glycosyldiacylglycerols; Lipid analysis. Bridgwater, The Oily Press, 2003, pp 137-180.
46. Grimm MO, Paetzold AJ, Zinser EG, Ruppert T, Hartmann T: Linking Alzheimer's disease, ß-amyloid, and lipids: A technical approach.; in Xia W, Xu H (eds): Amyloid precursor protein-a practical approach. Boca Raton, Florida, CRC Press, 2005, vol 129-144.
47. Yanagisawa K: Role of gangliosides in Alzheimer's disease. Biochim Biophys Acta 2007;1768:1943-1951. (Pubitemid 47125848)
48. Donoviel DB, Hadjantonakis AK, Ikeda M, Zheng H, Hyslop PS, Bernstein A: Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 1999;13:2801-2810.
49. Svennerholm L, Bostrom K, Fredman P, Mansson JE, Rosengren B, Rynmark BM: Human brain gangliosides: Developmental changes from early fetal stage to advanced age. Biochim Biophys Acta 1989;1005:109-117. (Pubitemid 19224675)
50. De Strooper B, Iwatsubo T, Wolfe MS: Presenilins and gamma-secretase: Structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med 2012;2:a006304.
51. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH: Beta-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 1995;81:525-531.
52. Heber S, Herms J, Gajic V, Hainfellner J, Aguzzi A, Rulicke T, von Kretzschmar H, von Koch C, Sisodia S, Tremml P, Lipp HP, Wolfer DP, Muller U: Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 2000;20:7951-7963.
53. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ, 3rd, Kandel ER, Duff K, Kirkwood A, Shen J: Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 2004;42:23-36. (Pubitemid 38456965)
54. Beglopoulos V, Sun X, Saura CA, Lemere CA, Kim RD, Shen J: Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J Biol Chem 2004;279:46907-46914. (Pubitemid 39518343)
55. Kracun I, Kalanj S, Talan-Hranilovic J, Cosovic C: Cortical distribution of gangliosides in Alzheimer's disease. Neurochem Int 1992;20:433-438.
56. Bertram L, Tanzi RE: Thirty years of Alzheimer's disease genetics: The implications of systematic meta-analyses. Nat Rev Neurosci 2008;9:768-778.
57. Bekris LM, Yu CE, Bird TD, Tsuang DW: Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 2010;23:213-227.
58. Haass C, Lemere CA, Capell A, Citron M, Seubert P, Schenk D, Lannfelt L, Selkoe DJ: The swedish mutation causes early-onset Alzheimer's disease by beta-secretase cleavage within the secretory pathway. Nat Med 1995;1:1291-1296.
59. Reaume AG, Howland DS, Trusko SP, Savage MJ, Lang DM, Greenberg BD, Siman R, Scott RW: Enhanced amyloidogenic processing of the beta-amyloid precursor protein in gene-targeted mice bearing the swedish familial Alzheimer's disease mutations and a "humanized" abeta sequence. J Biol Chem 1996;271:23380-23388. (Pubitemid 26314785)
60. Thinakaran G, Teplow DB, Siman R, Greenberg B, Sisodia SS: Metabolism of the "swedish" amyloid precursor protein variant in neuro2a (n2a) cells. Evidence that cleavage at the "beta-secretase" site occurs in the golgi apparatus. J Biol Chem 1996;271:9390-9397.
61. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ: Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 1992;360:672-674. (Pubitemid 23007680)
62. Oikawa N, Goto M, Ikeda K, Taguchi R, Yanagisawa K: The gamma-secretase inhibitor dapt increases the levels of gangliosides at neuritic terminals of differentiating pc12 cells. Neurosci Lett 2012;525:49-53.
63. von Rotz RC, Kohli BM, Bosset J, Meier M, Suzuki T, Nitsch RM, Konietzko U: The app intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor. J Cell Sci 2004;117:4435-4448. (Pubitemid 39360070)
64. Ohkawara T, Nagase H, Koh CS, Nakayama K: The amyloid precursor protein intracellular domain alters gene expression and induces neuron-specific apoptosis. Gene 2011;475:1-9.
65. Hong Y, Beckett C, Belyaev ND, Turner AJ: The impact of amyloid precursor protein signalling and histone deacetylase inhibition on neprilysin expression in human prostate cells. Int J Cancer 2012;130:775-786.
66. Soderberg M, Edlund C, Kristensson K, Dallner G: Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 1991;26:421-425.
67. Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ: Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: A case-control study. Br J Nutr 2003;89:483-489. (Pubitemid 36582118)
68. Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G: Amyloid precursor protein regulates brain apolipoprotein e and cholesterol metabolism through lipoprotein receptor lrp1. Neuron 2007;56:66-78. (Pubitemid 47484175)
69. Grimm MO, Mett J, Stahlmann CP, Haupenthal VJ, Zimmer VC, Hartmann T: Neprilysin and abeta clearance: Impact of the app intracellular domain in nep regulation and implications in Alzheimer's disease. Front Aging Neurosci 2013;5:98.
70. Ichikawa S, Ozawa K, Hirabayashi Y: Molecular cloning and characterization of the mouse ceramide glucosyltransferase gene. Biochem Biophys Res Commun 1998;253:707-711. (Pubitemid 29039206)
71. Uchida Y, Itoh M, Taguchi Y, Yamaoka S, Umehara H, Ichikawa S, Hirabayashi Y, Holleran WM, Okazaki T: Ceramide reduction and transcriptional up-regulation of glucosylceramide synthase through doxorubicin-activated sp1 in drug-resistant hl-60/adr cells. Cancer Res 2004;64:6271-6279. (Pubitemid 39129431)
72. Yu RK, Bieberich E, Xia T, Zeng G: Regulation of ganglioside biosynthesis in the nervous system. J Lipid Res 2004;45:783-793. (Pubitemid 38552848)
73. Zinser EG, Hartmann T, Grimm MO: Amyloid beta-protein and lipid metabolism. Biochim Biophys Acta 2007;1768:1991-2001. (Pubitemid 47161020)
74. Geekiyanage H, Chan C: Microrna-137/181c regulates serine palmitoyltransferase and in turn amyloid beta, novel targets in sporadic Alzheimer's disease. J Neurosci 2011;31:14820-14830.
75. Kolter T, Proia RL, Sandhoff K: Combinatorial ganglioside biosynthesis. J Biol Chem 2002;277:25859-25862. (Pubitemid 34967063)
76. Wiley JC, Hudson M, Kanning KC, Schecterson LC, Bothwell M: Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment. J Neurochem 2005;94:1189-1201. (Pubitemid 41232575)
77. Walker ES, Martinez M, Brunkan AL, Goate A: Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in abeta 42/40 ratios. J Neurochem 2005;92:294-301. (Pubitemid 40194020)
78. Mutoh T, Kawamura N, Hirabayashi Y, Shima S, Miyashita T, Ito S, Asakura K, Araki W, Cazzaniga E, Muto E, Masserini M: Abnormal cross-talk between mutant presenilin 1 (i143t, g384a) and glycosphingolipid biosynthesis. FASEB J 2012;26:3065-3074.
79. Marcus DL, Strafaci JA, Miller DC, Masia S, Thomas CG, Rosman J, Hussain S, Freedman ML: Quantitative neuronal c-fos and c-jun expression in Alzheimer's disease. Neurobiol Aging 1998;19:393-400. (Pubitemid 29065488)
80. Crespo PM, Silvestre DC, Gil GA, Maccioni HJ, Daniotti JL, Caputto BL: C-fos activates glucosylceramide synthase and glycolipid synthesis in pc12 cells. J Biol Chem 2008;283:31163-31171.
81. Niimi K, Nishioka C, Miyamoto T, Takahashi E, Miyoshi I, Itakura C, Yamashita T: Impairment of neuropsychological behaviors in ganglioside gm3-knockout mice. Biochem Biophys Res Commun 2011;406:524-528.
82. Wu G, Lu ZH, Kulkarni N, Amin R, Ledeen RW: Mice lacking major brain gangliosides develop Parkinsonism. Neurochem Res 2011;36:1706-1714.
83. Ohmi Y, Tajima O, Ohkawa Y, Yamauchi Y, Sugiura Y, Furukawa K: Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: Elucidation by a series of ganglioside-deficient mutant mice. J Neurochem 2011;116:926-935.
84. Prestia A, Baglieri A, Pievani M, Bonetti M, Rasser PE, Thompson PM, Marino S, Bramanti P, Frisoni GB: The in vivo topography of cortical changes in healthy aging and prodromal Alzheimer's disease. Supplements to Clin Neurophysiol 2013;62:67-80.
85. Sturm VE, Yokoyama JS, Seeley WW, Kramer JH, Miller BL, Rankin KP: Heightened emotional contagion in mild cognitive impairment and Alzheimer's disease is associated with temporal lobe degeneration. Proc Natl Acad Sci U S A 2013;110:9944-9949.
86. Larner AJ: The cerebellum in Alzheimer's disease. Dement Geriatr Cogn Disord 1997;8:203-209. (Pubitemid 27243704)
87. Kracun I, Rosner H, Cosovic C, Stavljenic A: Topographical atlas of the gangliosides of the adult human brain. J Neurochem 1984;43:979-989. (Pubitemid 14011251)
88. Marks N, Berg MJ, Saito M: Glucosylceramide synthase decrease in frontal cortex of Alzheimer brain correlates with abnormal increase in endogenous ceramides: Consequences to morphology and viability on enzyme suppression in cultured primary neurons. Brain Res 2008;1191:136-147.
89. Bernardo A, Harrison FE, McCord M, Zhao J, Bruchey A, Davies SS, Jackson Roberts L 2nd, Mathews PM, Matsuoka Y, Ariga T, Yu RK, Thompson R, McDonald MP: Elimination of gd3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 2009;30:1777-1791.
90. Tamboli IY, Prager K, Barth E, Heneka M, Sandhoff K, Walter J: Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. J Biol Chem 2005;280:28110-28117. (Pubitemid 41076929)