Lipid Rafts in Neurodegeneration and Neuroprotection

Molecular Neurobiology

Volumn 50, Issue 1, 2014, Pages 130-148

  Sonnino, Sandro ^a   Aureli, Massimo ^a   Grassi, Sara ^a   Mauri, Laura ^a   Prioni, Simona ^a   Prinetti, Alessandro ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Cholesterol; Gangliosides; Lipid rafts; Liquid ordered phase; Sphingolipids

Indexed keywords

AMYLOID PROTEIN; LIPID; MYELIN;

ALZHEIMER DISEASE; CELL COMPARTMENTALIZATION; DISEASE ASSOCIATION; HUMAN; LIPID BILAYER; LIPID COMPOSITION; LIPID RAFT; NERVE DEGENERATION; NERVOUS SYSTEM; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PHASE SEPARATION; PROTEIN PROCESSING; REGULATORY MECHANISM; REVIEW; ANIMAL; CELL MEMBRANE; DEGENERATIVE DISEASE; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CELL MEMBRANE; HUMANS; MEMBRANE MICRODOMAINS; NEURODEGENERATIVE DISEASES; SIGNAL TRANSDUCTION;

EID: 84910137292     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-013-8614-4     Document Type: Review

References (289)

1. IUPAC–IUBMB, JCoBN (1998) Nomenclature of glycolipids. Carbohydr Res 312:167–175
2. Sonnino S, Prinetti A (2013) Membrane domains and the “lipid raft” concept. Curr Med Chem 20:4–21
3. Cantu L, Del Favero E, Sonnino S, Prinetti A (2011) Gangliosides and the multiscale modulation of membrane structure. Chem Phys Lipids 164:796–810
4. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731
5. Steim JM, Tourtellotte ME, Reinert JC, McElhaney RN, Rader RL (1969) Calorimetric evidence for the liquid-crystalline state of lipids in a biomembrane. Proc Natl Acad Sci U S A 63:104–109
6. Kucerka N, Tristram-Nagle S, Nagle JF (2006) Closer look at structure of fully hydrated fluid phase DPPC bilayers. Biophys J 90:L83–L85
7. Lindner R, Naim HY (2009) Domains in biological membranes. Exp Cell Res 315:2871–2878
8. Kusumi A, Fujiwara TK, Chadda R, Xie M, Tsunoyama TA, Kalay Z, Kasai RS, Suzuki KG (2012) Dynamic organizing principles of the plasma membrane that regulate signal transduction: commemorating the fortieth anniversary of Singer and Nicolson’s fluid-mosaic model. Annu Rev Cell Dev Biol 28:215–250
9. van Meer G, de Kroon AI (2011) Lipid map of the mammalian cell. J Cell Sci 124:5–8
10. Merrill AH Jr (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev 111:6387–6422
11. Sullards MC, Liu Y, Chen Y, Merrill AH Jr (2011) Analysis of mammalian sphingolipids by liquid chromatography tandem mass spectrometry (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). Biochim Biophys Acta 1811:838–853
12. Mullen TD, Hannun YA, Obeid LM (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 441:789–802
13. Sandhoff R (2010) Very long chain sphingolipids: tissue expression, function and synthesis. FEBS Lett 584:1907–1913
14. Pruett ST, Bushnev A, Hagedorn K, Adiga M, Haynes CA, Sullards MC, Liotta DC, Merrill AH Jr (2008) Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols. J Lipid Res 49:1621–1639
15. Sonnino S, Chigorno V (2000) Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures. Biochim Biophys Acta 1469:63–77
16. Piccinini M, Scandroglio F, Prioni S, Buccinna B, Loberto N, Aureli M, Chigorno V, Lupino E, DeMarco G, Lomartire A, Rinaudo MT, Sonnino S, Prinetti A (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41:314–340
17. Aureli M, Loberto N, Lanteri P, Chigorno V, Prinetti A, Sonnino S (2011) Cell surface sphingolipid glycohydrolases in neuronal differentiation and aging in culture. J Neurochem 116:891–899
18. Yu RK, Nakatani Y, Yanagisawa M (2009) The role of glycosphingolipid metabolism in the developing brain. J Lipid Res 50:S440–S445
19. Tidhar R, Futerman AH (2013) The complexity of sphingolipid biosynthesis in the endoplasmic reticulum. Biochim Biophys Acta 1833:2511–2518
20. van Meer G, Hoetzl S (2010) Sphingolipid topology and the dynamic organization and function of membrane proteins. FEBS Lett 584:1800–1805
21. Haughey NJ (2010) Sphingolipids in neurodegeneration. Neuromol Med 12:301–305
22. Marin R, Rojo JA, Fabelo N, Fernandez CE, Diaz M (2013) Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis? Neuroscience 245:26–39
23. Reitz C (2013) Dyslipidemia and the risk of Alzheimer’s disease. Curr Atheroscler Rep 15:307
24. Lee AG, Birdsall NJ, Metcalfe JC, Toon PA, Warren GB (1974) Clusters in lipid bilayers and the interpretation of thermal effects in biological membranes. Biochemistry 13:3699–3705
25. Wunderlich F, Ronai A, Speth V, Seelig J, Blume A (1975) Thermotropic lipid clustering in tetrahymena membranes. Biochemistry 14:3730–3735
26. Wunderlich F, Ronai A (1975) Adaptive lowering of the lipid clustering temperature within Tetrahymena membranes. FEBS Lett 55:237–241
27. Wunderlich F, Kreutz W, Mahler P, Ronai A, Heppeler G (1978) Thermotropic fluid goes to ordered “discontinuous” phase separation in microsomal lipids of Tetrahymena. An X-ray diffraction study. Biochemistry 17:2005–2010
28. Karnovsky MJ, Kleinfeld AM, Hoover RL, Klausner RD (1982) The concept of lipid domains in membranes. J Cell Biol 94:1–6
29. Koynova R, Caffrey M (1998) Phases and phase transitions of the phosphatidylcholines. Biochim Biophys Acta 1376:91–145
30. Caffrey M, Kerr DS, Feng L, Koynova R, Ding L (1998) LIPIDAT: a web-based relational database of lipid phase transition types, temperatures, enthalpy changes and molecular structures. Biophys J 74:A315–A315
31. Koynova R, Caffrey M (1995) Phases and phase transitions of the sphingolipids. Biochim Biophys Acta 1255:213–236
32. Goni FM, Alonso A, Bagatolli LA, Brown RE, Marsh D, Prieto M, Thewalt JL (2008) Phase diagrams of lipid mixtures relevant to the study of membrane rafts. Biochim Biophys Acta 1781:665–684
33. Westerlund B, Slotte JP (2009) How the molecular features of glycosphingolipids affect domain formation in fluid membranes. Biochim Biophys Acta 1788:194–201
34. Elson EL, Fried E, Dolbow JE, Genin GM (2010) Phase separation in biological membranes: integration of theory and experiment. Annu Rev Biophys 39:207–226
35. Prinetti A, Chigorno V, Prioni S, Loberto N, Marano N, Tettamanti G, Sonnino S (2001) Changes in the lipid turnover, composition, and organization, as sphingolipid-enriched membrane domains, in rat cerebellar granule cells developing in vitro. J Biol Chem 276:21136–21145
36. O’Brien JS, Sampson EL (1965) Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter, and myelin. J Lipid Res 6:545–551
37. Sastry PS (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24:69–176
38. O’Brien JS, Sampson EL (1965) Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res 6:537–544
39. Prinetti A, Chigorno V, Tettamanti G, Sonnino S (2000) Sphingolipid-enriched membrane domains from rat cerebellar granule cells differentiated in culture. A compositional study. J Biol Chem 275:11658–11665
40. Mouritsen OG (2010) The liquid-ordered state comes of age. Biochim Biophys Acta 1798:1286–1288
41. Ipsen JH, Karlstrom G, Mouritsen OG, Wennerstrom H, Zuckermann MJ (1987) Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta 905:162–172
42. Bagatolli LA, Ipsen JH, Simonsen AC, Mouritsen OG (2010) An outlook on organization of lipids in membranes: searching for a realistic connection with the organization of biological membranes. Prog Lipid Res 49:378–389
43. Quinn PJ, Wolf C (2009) The liquid-ordered phase in membranes. Biochim Biophys Acta 1788:33–46
44. Sonnino S, Prinetti A (2010) Lipids and membrane lateral organization. Front Physiol 1:153
45. Fantini J, Barrantes FJ (2009) Sphingolipid/cholesterol regulation of neurotransmitter receptor conformation and function. Biochim Biophys Acta 1788:2345–2361
46. Pandit SA, Jakobsson E, Scott HL (2004) Simulation of the early stages of nano-domain formation in mixed bilayers of sphingomyelin, cholesterol, and dioleylphosphatidylcholine. Biophys J 87:3312–3322
47. Mombelli E, Morris R, Taylor W, Fraternali F (2003) Hydrogen-bonding propensities of sphingomyelin in solution and in a bilayer assembly: a molecular dynamics study. Biophys J 84:1507–1517
48. Pascher I (1976) Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability. Biochim Biophys Acta 455:433–451
49. van Meer G, Simons K (1988) Lipid polarity and sorting in epithelial cells. J Cell Biochem 36:51–58
50. Klemm RW, Ejsing CS, Surma MA, Kaiser HJ, Gerl MJ, Sampaio JL, de Robillard Q, Ferguson C, Proszynski TJ, Shevchenko A, Simons K (2009) Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network. J Cell Biol 185:601–612
51. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572
52. Sonnino S, Prinetti A (2008) Membrane lipid domains and membrane lipid domain preparations: are they the same thing? Trends Glycosci Glycotechnol 20:315–340
53. Lingwood D, Ries J, Schwille P, Simons K (2008) Plasma membranes are poised for activation of raft phase coalescence at physiological temperature. Proc Natl Acad Sci U S A 105:10005–10010
54. Kaiser HJ, Lingwood D, Levental I, Sampaio JL, Kalvodova L, Rajendran L, Simons K (2009) Order of lipid phases in model and plasma membranes. Proc Natl Acad Sci U S A 106:16645–16650
55. Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, von Middendorff C, Schonle A, Hell SW (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457:1159–1162
56. Belkind-Gerson J, Carreon-Rodriguez A, Contreras-Ochoa CO, Estrada-Mondaca S, Parra-Cabrera MS (2008) Fatty acids and neurodevelopment. J Pediatr Gastroenterol Nutr 47(Suppl 1):S7–S9
57. Iwabuchi K, Nakayama H, Masuda H, Kina K, Ogawa H, Takamori K (2012) Membrane microdomains in immunity: glycosphingolipid-enriched domain-mediated innate immune responses. Biofactors 38:275–283
58. Frisz JF, Lou K, Klitzing HA, Hanafin WP, Lizunov V, Wilson RL, Carpenter KJ, Kim R, Hutcheon ID, Zimmerberg J, Weber PK, Kraft ML (2013) Direct chemical evidence for sphingolipid domains in the plasma membranes of fibroblasts. Proc Natl Acad Sci U S A 110:E613–E622
59. Folch-Pi J (1968) The composition of nervous membranes. Prog Brain Res 29:1–17
60. Svennerholm L, Bostrom K, Jungbjer B, Olsson L (1994) Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem 63:1802–1811
61. Stoffel W, Bosio A (1997) Myelin glycolipids and their functions. Curr Opin Neurobiol 7:654–661
62. Aggarwal S, Yurlova L, Simons M (2011) Central nervous system myelin: structure, synthesis and assembly. Trends Cell Biol 21:585–593
63. Saher G, Quintes S, Nave KA (2011) Cholesterol: a novel regulatory role in myelin formation. Neuroscientist 17:79–93
64. Pfrieger FW, Ungerer N (2011) Cholesterol metabolism in neurons and astrocytes. Prog Lipid Res 50:357–371
65. Maccarrone M, Bernardi G, Agro AF, Centonze D (2011) Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for membrane fluidity disturbance. Br J Pharmacol 163:1379–1390
66. Levental I, Grzybek M, Simons K (2010) Greasing their way: lipid modifications determine protein association with membrane rafts. Biochemistry 49:6305–6316
67. Fantini J (2007) Interaction of proteins with lipid rafts through glycolipid-binding domains: biochemical background and potential therapeutic applications. Curr Med Chem 14:2911–2917
68. Yahi N, Aulas A, Fantini J (2010) How cholesterol constrains glycolipid conformation for optimal recognition of Alzheimer’s beta amyloid peptide (Abeta1-40). PLoS ONE 5:e9079
69. Fantini J, Yahi N (2010) Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases. Expert Rev Mol Med 12:e27
70. Fantini J, Carlus D, Yahi N (2011) The fusogenic tilted peptide (67-78) of alpha-synuclein is a cholesterol binding domain. Biochim Biophys Acta 1808:2343–2351
71. Fantini J, Yahi N (2011) Molecular basis for the glycosphingolipid-binding specificity of alpha-synuclein: key role of tyrosine 39 in membrane insertion. J Mol Biol 408:654–669
72. Baier CJ, Fantini J, Barrantes FJ (2012) Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor. Sci Rep 1:69
73. Chattopadhyay A, Paila YD, Shrivastava S, Tiwari S, Singh P, Fantini J (2012) Sphingolipid-binding domain in the serotonin (1A) receptor. Adv Exp Med Biol 749:279–293
74. Di Scala C, Yahi N, Lelievre C, Garmy N, Chahinian H, Fantini J (2013) Biochemical identification of a linear cholesterol-binding domain within Alzheimer’s beta amyloid peptide. ACS Chem Neurosci 4:509–517
75. Pryor S, McCaffrey G, Young LR, Grimes ML (2012) NGF causes TrkA to specifically attract microtubules to lipid rafts. PLoS ONE 7:e35163
76. Ichikawa N, Iwabuchi K, Kurihara H, Ishii K, Kobayashi T, Sasaki T, Hattori N, Mizuno Y, Hozumi K, Yamada Y, Arikawa-Hirasawa E (2009) Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth. J Cell Sci 122:289–299
77. Pereira DB, Chao MV (2007) The tyrosine kinase Fyn determines the localization of TrkB receptors in lipid rafts. J Neurosci 27:4859–4869
78. Sebastiao AM, Assaife-Lopes N, Diogenes MJ, Vaz SH, Ribeiro JA (2011) Modulation of brain-derived neurotrophic factor (BDNF) actions in the nervous system by adenosine A(2A) receptors and the role of lipid rafts. Biochim Biophys Acta 1808:1340–1349
79. Assaife-Lopes N, Sousa VC, Pereira DB, Ribeiro JA and Sebastiao AM (2013) Regulation of TrkB receptor translocation to lipid rafts by adenosine A receptors and its functional implications for BDNF-induced regulation of synaptic plasticity. Purinergic Signal (in press)
80. Saarma M (2001) GDNF recruits the signaling crew into lipid rafts. Trends Neurosci 24:427–429
81. Yang XL, Xiong WC, Mei L (2004) Lipid rafts in neuregulin signaling at synapses. Life Sci 75:2495–2504
82. Gauthier LR, Robbins SM (2003) Ephrin signaling: one raft to rule them all? One raft to sort them? One raft to spread their call and in signaling bind them? Life Sci 74:207–216
83. Bruckner K, Pablo Labrador J, Scheiffele P, Herb A, Seeburg PH, Klein R (1999) EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron 22:511–524
84. Dainese E, Oddi S, Maccarrone M (2010) Interaction of endocannabinoid receptors with biological membranes. Curr Med Chem 17:1487–1499
85. Xapelli S, Agasse F, Sarda-Arroyo L, Bernardino L, Santos T, Ribeiro FF, Valero J, Braganca J, Schitine C, de Melo Reis RA, Sebastiao AM, Malva JO (2013) Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures. PLoS ONE 8:e63529
86. D’Ambrosi N, Volonte C (2013) Metabotropic purinergic receptors in lipid membrane microdomains. Curr Med Chem 20:56–63
87. Fang J, Han D, Hong J, Tan Q, Tian Y (2012) The chemokine, macrophage inflammatory protein-2gamma, reduces the expression of glutamate transporter-1 on astrocytes and increases neuronal sensitivity to glutamate excitotoxicity. J Neuroinflammation 9:267
88. Lasley RD (2011) Adenosine receptors and membrane microdomains. Biochim Biophys Acta 1808:1284–1289
89. Assaife-Lopes N, Sousa VC, Pereira DB, Ribeiro JA, Chao MV, Sebastiao AM (2010) Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation. J Neurosci 30:8468–8480
90. Kumari R, Castillo C, Francesconi A (2013) Agonist-dependent signaling by group I metabotropic glutamate receptors is regulated by association with lipid domains. J Biol Chem 288:32004–32019
91. Padgett CL, Slesinger PA (2010) GABAB receptor coupling to G-proteins and ion channels. Adv Pharmacol 58:123–147
92. Chini B, Parenti M (2004) G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there? J Mol Endocrinol 32:325–338
93. Cole AA, Dosemeci A, Reese TS (2010) Co-segregation of AMPA receptors with G(M1) ganglioside in synaptosomal membrane subfractions. Biochem J 427:535–540
94. Delint-Ramirez I, Salcedo-Tello P, Bermudez-Rattoni F (2008) Spatial memory formation induces recruitment of NMDA receptor and PSD-95 to synaptic lipid rafts. J Neurochem 106:1658–1668
95. Francesconi A, Kumari R, Zukin RS (2009) Regulation of group I metabotropic glutamate receptor trafficking and signaling by the caveolar/lipid raft pathway. J Neurosci 29:3590–3602
96. Delint-Ramirez I, Fernandez E, Bayes A, Kicsi E, Komiyama NH, Grant SG (2010) In vivo composition of NMDA receptor signaling complexes differs between membrane subdomains and is modulated by PSD-95 and PSD-93. J Neurosci 30:8162–8170
97. Mukherjee A, Arnaud L, Cooper JA (2003) Lipid-dependent recruitment of neuronal Src to lipid rafts in the brain. J Biol Chem 278:40806–40814
98. Sekino-Suzuki N, Yuyama K, Miki T, Kaneda M, Suzuki H, Yamamoto N, Yamamoto T, Oneyama C, Okada M, Kasahara K (2013) Involvement of gangliosides in the process of Cbp/PAG phosphorylation by Lyn in developing cerebellar growth cones. J Neurochem 124:514–522
99. Scorticati C, Formoso K, Frasch AC (2011) Neuronal glycoprotein M6a induces filopodia formation via association with cholesterol-rich lipid rafts. J Neurochem 119:521–531
100. Zhao H, Cao X, Wu G, Loh HH, Law PY (2009) Neurite outgrowth is dependent on the association of c-Src and lipid rafts. Neurochem Res 34:2197–2205
101. Santuccione A, Sytnyk V, Leshchyns’ka I, Schachner M (2005) Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. J Cell Biol 169:341–354
102. Kasahara K, Watanabe Y, Yamamoto T, Sanai Y (1997) Association of Src family tyrosine kinase Lyn with ganglioside GD3 in rat brain. Possible regulation of Lyn by glycosphingolipid in caveolae-like domains. J Biol Chem 272:29947–29953
103. Kasahara K, Watanabe K, Kozutsumi Y, Oohira A, Yamamoto T, Sanai Y (2002) Association of GPI-anchored protein TAG-1 with src-family kinase Lyn in lipid rafts of cerebellar granule cells. Neurochem Res 27:823–829
104. Miki T, Kaneda M, Iida K, Hasegawa G, Murakami M, Yamamoto N, Asou H, Kasahara K (2013) An anti-sulfatide antibody O4 immunoprecipitates sulfatide rafts including Fyn, Lyn and the G protein alpha subunit in rat primary immature oligodendrocytes. Glycoconj J 30:819–823
105. Prinetti A, Prioni S, Chigorno V, Karagogeos D, Tettamanti G, Sonnino S (2001) Immunoseparation of sphingolipid-enriched membrane domains enriched in Src family protein tyrosine kinases and in the neuronal adhesion molecule TAG-1 by anti-GD3 ganglioside monoclonal antibody. J Neurochem 78:1162–1167
106. Ge X, Qiu Y, Loh HH, Law PY (2009) GRIN1 regulates micro-opioid receptor activities by tethering the receptor and G protein in the lipid raft. J Biol Chem 284:36521–36534
107. Grider MH, Park D, Spencer DM, Shine HD (2009) Lipid raft-targeted Akt promotes axonal branching and growth cone expansion via mTOR and Rac1, respectively. J Neurosci Res 87:3033–3042
108. Yuyama K, Sekino-Suzuki N, Sanai Y, Kasahara K (2007) Translocation of activated heterotrimeric G protein Galpha(o) to ganglioside-enriched detergent-resistant membrane rafts in developing cerebellum. J Biol Chem 282:26392–26400
109. Delling M, Wischmeyer E, Dityatev A, Sytnyk V, Veh RW, Karschin A, Schachner M (2002) The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts. J Neurosci 22:7154–7164
110. Kramer EM, Klein C, Koch T, Boytinck M, Trotter J (1999) Compartmentation of Fyn kinase with glycosylphosphatidylinositol-anchored molecules in oligodendrocytes facilitates kinase activation during myelination. J Biol Chem 274:29042–29049
111. Loberto N, Prioni S, Prinetti A, Ottico E, Chigorno V, Karagogeos D, Sonnino S (2003) The adhesion protein TAG-1 has a ganglioside environment in the sphingolipid-enriched membrane domains of neuronal cells in culture. J Neurochem 85:224–233
112. Rege TA, Hagood JS (2006) Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J 20:1045–1054
113. Suzuki T, Du F, Tian QB, Zhang J, Endo S (2008) Ca2+/calmodulin-dependent protein kinase IIalpha clusters are associated with stable lipid rafts and their formation traps PSD-95. J Neurochem 104:596–610
114. Sebastiao AM, Colino-Oliveira M, Assaife-Lopes N, Dias RB, Ribeiro JA (2013) Lipid rafts, synaptic transmission and plasticity: impact in age-related neurodegenerative diseases. Neuropharmacology 64:97–107
115. Yoon SJ, Nakayama K, Takahashi N, Yagi H, Utkina N, Wang HY, Kato K, Sadilek M, Hakomori SI (2006) Interaction of N-linked glycans, having multivalent GlcNAc termini, with GM3 ganglioside. Glycoconj J 23:639–649
116. Yoon SJ, Nakayama K, Hikita T, Handa K, Hakomori SI (2006) Epidermal growth factor receptor tyrosine kinase is modulated by GM3 interaction with N-linked GlcNAc termini of the receptor. Proc Natl Acad Sci U S A 103:18987–18991
117. Coskun U, Grzybek M, Drechsel D, Simons K (2011) Regulation of human EGF receptor by lipids. Proc Natl Acad Sci U S A 108:9044–9048
118. Favaron M, Manev H, Alho H, Bertolino M, Ferret B, Guidotti A, Costa E (1988) Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex. Proc Natl Acad Sci U S A 85:7351–7355
119. Skaper SD, Facci L, Milani D, Leon A (1989) Monosialoganglioside GM1 protects against anoxia-induced neuronal death in vitro. Exp Neurol 106:297–305
120. Ferrari G, Anderson BL, Stephens RM, Kaplan DR, Greene LA (1995) Prevention of apoptotic neuronal death by GM1 ganglioside. Involvement of Trk neurotrophin receptors. J Biol Chem 270:3074–3080
121. Ferrari G, Batistatou A, Greene LA (1993) Gangliosides rescue neuronal cells from death after trophic factor deprivation. J Neurosci 13:1879–1887
122. Prinetti A, Iwabuchi K, Hakomori S (1999) Glycosphingolipid-enriched signaling domain in mouse neuroblastoma Neuro2a cells. Mechanism of ganglioside-dependent neuritogenesis. J Biol Chem 274:20916–20924
123. Hadjiconstantinou M, Neff NH (1998) GM1 ganglioside: in vivo and in vitro trophic actions on central neurotransmitter systems. J Neurochem 70:1335–1345
124. Bachis A, Rabin SJ, Del Fiacco M, Mocchetti I (2002) Gangliosides prevent excitotoxicity through activation of TrkB receptor. Neurotox Res 4:225–234
125. Rabin SJ, Bachis A, Mocchetti I (2002) Gangliosides activate Trk receptors by inducing the release of neurotrophins. J Biol Chem 277:49466–49472
126. Rabin SJ, Mocchetti I (1995) GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 65:347–354
127. Farooqui T, Franklin T, Pearl DK, Yates AJ (1997) Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J Neurochem 68:2348–2355
128. Mutoh T, Tokuda A, Miyadai T, Hamaguchi M, Fujiki N (1995) Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc Natl Acad Sci U S A 92:5087–5091
129. Duchemin AM, Ren Q, Neff NH, Hadjiconstantinou M (2008) GM1-induced activation of phosphatidylinositol 3-kinase: involvement of Trk receptors. J Neurochem 104:1466–1477
130. Duchemin AM, Ren Q, Mo L, Neff NH, Hadjiconstantinou M (2002) GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain. J Neurochem 81:696–707
131. Mo L, Ren Q, Duchemin AM, Neff NH, Hadjiconstantinou M (2005) GM1 and ERK signaling in the aged brain. Brain Res 1054:125–134
132. Guirland C, Suzuki S, Kojima M, Lu B, Zheng JQ (2004) Lipid rafts mediate chemotropic guidance of nerve growth cones. Neuron 42:51–62
133. Suzuki S, Numakawa T, Shimazu K, Koshimizu H, Hara T, Hatanaka H, Mei L, Lu B, Kojima M (2004) BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation. J Cell Biol 167:1205–1215
134. Hibbert AP, Kramer BM, Miller FD, Kaplan DR (2006) The localization, trafficking and retrograde transport of BDNF bound to p75NTR in sympathetic neurons. Mol Cell Neurosci 32:387–402
135. Mihara T, Ueda A, Hirayama M, Takeuchi T, Yoshida S, Naito K, Yamamoto H, Mutoh T (2006) Detection of new anti-neutral glycosphingolipids antibodies and their effects on Trk neurotrophin receptors. FEBS Lett 580:4991–4995
136. Mojsilovic-Petrovic J, Jeong GB, Crocker A, Arneja A, David S, Russell DS, Kalb RG (2006) Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors. J Neurosci 26:9250–9263
137. Mutoh T, Hamano T, Tokuda A, Kuriyama M (2000) Unglycosylated Trk protein does not co-localize nor associate with ganglioside GM1 in stable clone of PC12 cells overexpressing Trk (PCtrk cells). Glycoconj J 17:233–237
138. Hasegawa T, Yamaguchi K, Wada T, Takeda A, Itoyama Y, Miyagi T (2000) Molecular cloning of mouse ganglioside sialidase and its increased expression in neuro2a cell differentiation. J Biol Chem 275:14778
139. Da Silva JS, Hasegawa T, Miyagi T, Dotti CG, Abad-Rodriguez J (2005) Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nat Neurosci 8:606–615
140. Ueda A, Shima S, Miyashita T, Ito S, Ueda M, Kusunoki S, Asakura K, Mutoh T (2010) Anti-GM1 antibodies affect the integrity of lipid rafts. Mol Cell Neurosci 45:355–362
141. Paratcha G, Ibanez CF (2002) Lipid rafts and the control of neurotrophic factor signaling in the nervous system: variations on a theme. Curr Opin Neurobiol 12:542–549
142. Tsui-Pierchala BA, Encinas M, Milbrandt J, Johnson EM Jr (2002) Lipid rafts in neuronal signaling and function. Trends Neurosci 25:412–417
143. Nagappan G, Lu B (2005) Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci 28:464–471
144. Kasahara K, Watanabe K, Takeuchi K, Kaneko H, Oohira A, Yamamoto T, Sanai Y (2000) Involvement of gangliosides in glycosylphosphatidylinositol-anchored neuronal cell adhesion molecule TAG-1 signaling in lipid rafts. J Biol Chem 275:34701–34709
145. Tansey MG, Baloh RH, Milbrandt J, Johnson EM Jr (2000) GFRalpha-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival. Neuron 25:611–623
146. Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibanez CF (2001) Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron 29:171–184
147. Yang J, Lindahl M, Lindholm P, Virtanen H, Coffey E, Runeberg-Roos P, Saarma M (2004) PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth. FEBS Lett 569:267–271
148. Pierchala BA, Milbrandt J, Johnson EM Jr (2006) Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation. J Neurosci 26:2777–2787
149. Lundgren TK, Luebke M, Stenqvist A, Ernfors P (2008) Differential membrane compartmentalization of Ret by PTB-adaptor engagement. FEBS J 275:2055–2066
150. Lynch SA, Brugge JS, Levine JM (1986) Induction of altered c-src product during neural differentiation of embryonal carcinoma cells. Science 234:873–876
151. Mellstrom K, Bjelfman C, Hammerling U, Pahlman S (1987) Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation. Mol Cell Biol 7:4178–4184
152. Bjelfman C, Meyerson G, Cartwright CA, Mellstrom K, Hammerling U, Pahlman S (1990) Early activation of endogenous pp60src kinase activity during neuronal differentiation of cultured human neuroblastoma cells. Mol Cell Biol 10:361–370
153. den Hertog J, Pals CE, Peppelenbosch MP, Tertoolen LG, de Laat SW, Kruijer W (1993) Receptor protein tyrosine phosphatase alpha activates pp 60c-src and is involved in neuronal differentiation. EMBO J 12:3789–3798
154. Chakraborty M, Anderson GM, Chakraborty A, Chatterjee D (1993) Accumulation of high level of pp 60c-srcN is an early event during GM3-antibody mediated differentiation of neuro-2a neuroblastoma cells. Brain Res 625:197–202
155. Cartwright CA, Simantov R, Kaplan PL, Hunter T, Eckhart W (1987) Alterations in pp 60c-src accompany differentiation of neurons from rat embryo striatum. Mol Cell Biol 7:1830–1840
156. Yu XM, Salter MW (1999) Src, a molecular switch governing gain control of synaptic transmission mediated by N-methyl-d-aspartate receptors. Proc Natl Acad Sci U S A 96:7697–7704
157. Foster-Barber A, Bishop JM (1998) Src interacts with dynamin and synapsin in neuronal cells. Proc Natl Acad Sci U S A 95:4673–4677
158. Loberto N, Prioni S, Bettiga A, Chigorno V, Prinetti A, Sonnino S (2005) The membrane environment of endogenous cellular prion protein in primary rat cerebellar neurons. J Neurochem 95:771–783
159. Kamiguchi H (2006) The region-specific activities of lipid rafts during axon growth and guidance. J Neurochem 98:330–335
160. Guirland C, Zheng JQ (2007) Membrane lipid rafts and their role in axon guidance. Adv Exp Med Biol 621:144–155
161. Stuermer CA (2011) Microdomain-forming proteins and the role of the reggies/flotillins during axon regeneration in zebrafish. Biochim Biophys Acta 1812:415–422
162. McKerracher L (2002) Ganglioside rafts as MAG receptors that mediate blockade of axon growth. Proc Natl Acad Sci U S A 99:7811–7813
163. Labasque M, Faivre-Sarrailh C (2010) GPI-anchored proteins at the node of Ranvier. FEBS Lett 584:1787–1792
164. Boggs JM, Gao W, Zhao J, Park HJ, Liu Y, Basu A (2010) Participation of galactosylceramide and sulfatide in glycosynapses between oligodendrocyte or myelin membranes. FEBS Lett 584:1771–1778
165. Eckhardt M (2008) The role and metabolism of sulfatide in the nervous system. Mol Neurobiol 37:93–103
166. Marcus J, Popko B (2002) Galactolipids are molecular determinants of myelin development and axo-glial organization. Biochim Biophys Acta 1573:406–413
167. Bosio A, Binczek E, Stoffel W (1996) Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis. Proc Natl Acad Sci U S A 93:13280–13285
168. Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86:209–219
169. Hirahara Y, Bansal R, Honke K, Ikenaka K, Wada Y (2004) Sulfatide is a negative regulator of oligodendrocyte differentiation: development in sulfatide-null mice. Glia 45:269–277
170. Fewou SN, Fernandes A, Stockdale K, Francone VP, Dupree JL, Rosenbluth J, Pfeiffer SE, Bansal R (2010) Myelin protein composition is altered in mice lacking either sulfated or both sulfated and non-sulfated galactolipids. J Neurochem 112:599–610
171. Boggs JM, Gao W, Hirahara Y (2008) Myelin glycosphingolipids, galactosylceramide and sulfatide, participate in carbohydrate-carbohydrate interactions between apposed membranes and may form glycosynapses between oligodendrocyte and/or myelin membranes. Biochim Biophys Acta 1780:445–455
172. Taylor CM, Coetzee T, Pfeiffer SE (2002) Detergent-insoluble glycosphingolipid/cholesterol microdomains of the myelin membrane. J Neurochem 81:993–1004
173. Pan B, Fromholt SE, Hess EJ, Crawford TO, Griffin JW, Sheikh KA, Schnaar RL (2005) Myelin-associated glycoprotein and complementary axonal ligands, gangliosides, mediate axon stability in the CNS and PNS: neuropathology and behavioral deficits in single- and double-null mice. Exp Neurol 195:208–217
174. Schnaar RL, Lopez PH (2009) Myelin-associated glycoprotein and its axonal receptors. J Neurosci Res 87:3267–3276
175. McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13:805–811
176. Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757–767
177. Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617–627
178. Vinson M, Strijbos PJ, Rowles A, Facci L, Moore SE, Simmons DL, Walsh FS (2001) Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition. J Biol Chem 276:20280–20285
179. Vyas AA, Patel HV, Fromholt SE, Heffer-Lauc M, Vyas KA, Dang J, Schachner M, Schnaar RL (2002) Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci U S A 99:8412–8417
180. Domeniconi M, Cao Z, Spencer T, Sivasankaran R, Wang K, Nikulina E, Kimura N, Cai H, Deng K, Gao Y, He Z, Filbin M (2002) Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35:283–290
181. Liu BP, Fournier A, GrandPre T, Strittmatter SM (2002) Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science 297:1190–1193
182. Cao Z, Gao Y, Deng K, Williams G, Doherty P, Walsh FS (2009) Receptors for myelin inhibitors: structures and therapeutic opportunities. Mol Cell Neurosci 43:1–14
183. Venkatesh K, Chivatakarn O, Lee H, Joshi PS, Kantor DB, Newman BA, Mage R, Rader C, Giger RJ (2005) The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 25:808–822
184. Cao Z, Qiu J, Domeniconi M, Hou J, Bryson JB, Mellado W, Filbin MT (2007) The inhibition site on myelin-associated glycoprotein is within Ig-domain 5 and is distinct from the sialic acid binding site. J Neurosci 27:9146–9154
185. Simons K, Gerl MJ (2010) Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol 11:688–699
186. Aveldano MI, Bazan NG (1975) Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia. J Neurochem 25:919–920
187. Schengrund CL, Rosenberg A (1970) Intracellular location and properties of bovine brain sialidase. J Biol Chem 245:6196–6200
188. Tettamanti G, Morgan IG, Gombos G, Vincendon G, Mandel P (1972) Sub-synaptosomal localization of brain particulate neuraminidose. Brain Res 47:515–518
189. Tettamanti G, Preti A, Lombardo A, Suman T, Zambotti V (1975) Membrane-bound neuraminidase in the brain of different animals: behaviour of the enzyme on endogenous sialo derivatives and rationale for its assay. J Neurochem 25:451–456
190. Tettamanti G, Preti A, Lombardo A, Bonali F, Zambotti V (1973) Parallelism of subcellular location of major particulate neuraminidase and gangliosides in rabbit brain cortex. Biochim Biophys Acta 306:466–477
191. Preti A, Fiorilli A, Lombardo A, Caimi L, Tettamanti G (1980) Occurrence of sialyltransferase activity in the synaptosomal membranes prepared from calf brain cortex. J Neurochem 35:281–296
192. Magini A, Polchi A, Urbanelli L, Cesselli D, Beltrami A, Tancini B, Emiliani C (2013) TFEB activation promotes the recruitment of lysosomal glycohydrolases beta-hexosaminidase and beta-galactosidase to the plasma membrane. Biochem Biophys Res Commun 440:251–257
193. Aureli M, Masilamani AP, Illuzzi G, Loberto N, Scandroglio F, Prinetti A, Chigorno V, Sonnino S (2009) Activity of plasma membrane beta-galactosidase and beta-glucosidase. FEBS Lett 583:2469–2473
194. Aureli M, Loberto N, Bassi R, Ferraretto A, Perego S, Lanteri P, Chigorno V, Sonnino S, Prinetti A (2012) Plasma membrane-associated glycohydrolases activation by extracellular acidification due to proton exchangers. Neurochem Res 37:1296–1307
195. Crespo PM, Demichelis VT, Daniotti JL (2010) Neobiosynthesis of glycosphingolipids by plasma membrane-associated glycosyltransferases. J Biol Chem 285:29179–29190
196. Iwamori M, Iwamori Y (2005) Changes in the glycolipid composition and characteristic activation of GM3 synthase in the thymus of mouse after administration of dexamethasone. Glycoconj J 22:119–126
197. Aureli M, Gritti A, Bassi R, Loberto N, Ricca A, Chigorno V, Prinetti A, Sonnino S (2012) Plasma membrane-associated glycohydrolases along differentiation of murine neural stem cells. Neurochem Res 37:1344–1354
198. Prinetti A, Chigorno V, Mauri L, Loberto N, Sonnino S (2007) Modulation of cell functions by glycosphingolipid metabolic remodeling in the plasma membrane. J Neurochem 103(Suppl 1):113–125
199. Cremesti AE, Goni FM, Kolesnick R (2002) Role of sphingomyelinase and ceramide in modulating rafts: do biophysical properties determine biologic outcome? FEBS Lett 531:47–53
200. Horres CR, Hannun YA (2012) The roles of neutral sphingomyelinases in neurological pathologies. Neurochem Res 37:1137–1149
201. Milhas D, Clarke CJ, Hannun YA (2010) Sphingomyelin metabolism at the plasma membrane: implications for bioactive sphingolipids. FEBS Lett 584:1887–1894
202. Valaperta R, Chigorno V, Basso L, Prinetti A, Bresciani R, Preti A, Miyagi T, Sonnino S (2006) Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts. FASEB J 20:1227–1229
203. van Blitterswijk WJ, van der Luit AH, Veldman RJ, Verheij M, Borst J (2003) Ceramide: second messenger or modulator of membrane structure and dynamics? Biochem J 369:199–211
204. Stancevic B, Kolesnick R (2010) Ceramide-rich platforms in transmembrane signaling. FEBS Lett 584:1728–1740
205. Grassme H, Riethmuller J, Gulbins E (2007) Biological aspects of ceramide-enriched membrane domains. Prog Lipid Res 46:161–170
206. Mesmin B, Maxfield FR (2009) Intracellular sterol dynamics. Biochim Biophys Acta 1791:636–645
207. Lindblom G, Oradd G (2009) Lipid lateral diffusion and membrane heterogeneity. Biochim Biophys Acta 1788:234–244
208. Wood WG, Igbavboa U, Muller WE, Eckert GP (2011) Cholesterol asymmetry in synaptic plasma membranes. J Neurochem 116:684–689
209. Ottico E, Prinetti A, Prioni S, Giannotta C, Basso L, Chigorno V, Sonnino S (2003) Dynamics of membrane lipid domains in neuronal cells differentiated in culture. J Lipid Res 44:2142–2151
210. Burns MP, Igbavboa U, Wang L, Wood WG, Duff K (2006) Cholesterol distribution, not total levels, correlate with altered amyloid precursor protein processing in statin-treated mice. Neuromol Med 8:319–328
211. Williams JA, Batten SE, Harris M, Rockett BD, Shaikh SR, Stillwell W, Wassall SR (2012) Docosahexaenoic and Eicosapentaenoic Acids Segregate Differently between Raft and Nonraft Domains. Biophys J 103:228–237
212. Massey JB (2006) Membrane and protein interactions of oxysterols. Curr Opin Lipidol 17:296–301
213. Rimmerman N, Bradshaw HB, Kozela E, Levy R, Juknat A, Vogel Z (2012) Compartmentalization of endocannabinoids into lipid rafts in a microglial cell line devoid of caveolin-1. Br J Pharmacol 165:2436–2449
214. Rimmerman N, Hughes HV, Bradshaw HB, Pazos MX, Mackie K, Prieto AL, Walker JM (2008) Compartmentalization of endocannabinoids into lipid rafts in a dorsal root ganglion cell line. Br J Pharmacol 153:380–389
215. Ledesma MD, Martin MG, Dotti CG (2012) Lipid changes in the aged brain: effect on synaptic function and neuronal survival. Prog Lipid Res 51:23–35
216. Diaz ML, Fabelo N, Marin R (2012) Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice. Front Physiol 3:454
217. Fabelo N, Martin V, Marin R, Santpere G, Aso E, Ferrer I, Diaz M (2012) Evidence for premature lipid raft aging in APP/PS1 double-transgenic mice, a model of familial Alzheimer disease. J Neuropathol Exp Neurol 71:868–881
218. Marin R, Casanas V, Perez JA, Fabelo N, Fernandez C, Diaz M (2013) Oestrogens as modulators of neuronal signalosomes and brain lipid homeostasis related to protection against neurodegeneration. J Neuroendocrinol. doi:10.1111/jne.12068
219. Sandhoff K, Harzer K (2013) Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis. J Neurosci 33:10195–10208
220. Vitner EB, Futerman AH (2013) Neuronal forms of Gaucher disease. Handb Exp Pharmacol (216):405–419
221. Ledesma MD, Prinetti A, Sonnino S, Schuchman EH (2011) Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice. J Neurochem 116:779–788
222. Reddy A, Caler EV, Andrews NW (2001) Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Cell 106:157–169
223. Scandroglio F, Venkata JK, Loberto N, Prioni S, Schuchman EH, Chigorno V, Prinetti A, Sonnino S (2008) Lipid content of brain, brain membrane lipid domains, and neurons from acid sphingomyelinase deficient mice. J Neurochem 107:329–338
224. Buccinna B, Piccinini M, Prinetti A, Scandroglio F, Prioni S, Valsecchi M, Votta B, Grifoni S, Lupino E, Ramondetti C, Schuchman EH, Giordana MT, Sonnino S, Rinaudo MT (2009) Alterations of myelin-specific proteins and sphingolipids characterize the brains of acid sphingomyelinase-deficient mice, an animal model of Niemann-Pick disease type A. J Neurochem 109:105–115
225. Rosenbaum AI, Maxfield FR (2011) Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches. J Neurochem 116:789–795
226. Domon M, Nasir MN, Matar G, Pikula S, Besson F, Bandorowicz-Pikula J (2012) Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease. Cell Mol Life Sci 69:1773–1785
227. Rebeck GW, Kindy M, LaDu MJ (2002) Apolipoprotein E and Alzheimer’s disease: the protective effects of ApoE2 and E3. J Alzheimers Dis 4:145–154
228. Vance JE (2012) Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Model Mech 5:746–755
229. Zlokovic BV (2013) Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA Neurol 70:440–444
230. Holtzman DM, Herz J, Bu G (2012) Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006312
231. Vance JE, Campenot RB, Vance DE (2000) The synthesis and transport of lipids for axonal growth and nerve regeneration. Biochim Biophys Acta 1486:84–96
232. Posse De Chaves EI, Vance DE, Campenot RB, Kiss RS, Vance JE (2000) Uptake of lipoproteins for axonal growth of sympathetic neurons. J Biol Chem 275:19883–19890
233. Simons M, Lyons DA (2013) Axonal selection and myelin sheath generation in the central nervous system. Curr Opin Cell Biol 25:512–519
234. Block RC, Dorsey ER, Beck CA, Brenna JT, Shoulson I (2010) Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol 4:17–23
235. Karasinska JM, Hayden MR (2011) Cholesterol metabolism in Huntington disease. Nat Rev Neurol 7:561–572
236. Valenza M, Cattaneo E (2011) Emerging roles for cholesterol in Huntington’s disease. Trends Neurosci 34:474–486
237. Higatsberger MR, Sperk G, Bernheimer H, Shannak KS, Hornykiewicz O (1981) Striatal ganglioside levels in the rat following kainic acid lesions: comparison with Huntington’s disease. Exp Brain Res 44:93–96
238. Desplats PA, Denny CA, Kass KE, Gilmartin T, Head SR, Sutcliffe JG, Seyfried TN, Thomas EA (2007) Glycolipid and ganglioside metabolism imbalances in Huntington’s disease. Neurobiol Dis 27:265–277
239. Valencia A, Reeves PB, Sapp E, Li X, Alexander J, Kegel KB, Chase K, Aronin N, DiFiglia M (2010) Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington’s disease. J Neurosci Res 88:179–190
240. Gudala K, Bansal D, Muthyala H (2013) Role of serum cholesterol in Parkinson’s disease: a meta-analysis of evidence. J Parkinsons Dis 3:363–370
241. Kim KS, Kim JS, Park JY, Suh YH, Jou I, Joe EH, Park SM (2013) DJ-1 Associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes. Hum Mol Genet 22:4805–4817
242. Fallon L, Moreau F, Croft BG, Labib N, Gu WJ, Fon EA (2002) Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J Biol Chem 277:486–491
243. Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14:3477–3492
244. Martinez Z, Zhu M, Han S, Fink AL (2007) GM1 specifically interacts with alpha-synuclein and inhibits fibrillation. Biochemistry 46:1868–1877
245. Park JY, Kim KS, Lee SB, Ryu JS, Chung KC, Choo YK, Jou I, Kim J, Park SM (2009) On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft. J Neurochem 110:400–411
246. Fabelo N, Martin V, Santpere G, Marin R, Torrent L, Ferrer I, Diaz M (2011) Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Med 17:1107–1118
247. Silva T, Teixeira J, Remiao F, Borges F (2013) Alzheimer’s disease, cholesterol, and statins: the junctions of important metabolic pathways. Angew Chem Int Ed Engl 52:1110–1121
248. Maulik M, Westaway D, Jhamandas JH, Kar S (2013) Role of cholesterol in APP metabolism and its significance in Alzheimer’s disease pathogenesis. Mol Neurobiol 47:37–63
249. Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM, Kaddurah-Daouk R (2011) Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS ONE 6:e21643
250. Cheng H, Wang M, Li JL, Cairns NJ, Han X (2013) Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer’s disease: an early event in disease pathogenesis. J Neurochem 127:733–738
251. Ariga T, McDonald MP, Yu RK (2008) Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease–a review. J Lipid Res 49:1157–1175
252. Svennerholm L, Gottfries CG (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
253. Kalanj S, Kracun I, Rosner H, Cosovic C (1991) Regional distribution of brain gangliosides in Alzheimer’s disease. Neurol Croat 40:269–281
254. Brooksbank BW, McGovern J (1989) Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease. Mol Chem Neuropathol 11:143–156
255. Kracun I, Rosner H, Drnovsek V, Heffer-Lauc M, Cosovic C, Lauc G (1991) Human brain gangliosides in development, aging and disease. Int J Dev Biol 35:289–295
256. Kracun I, Kalanj S, Talan-Hranilovic J, Cosovic C (1992) Cortical distribution of gangliosides in Alzheimer’s disease. Neurochem Int 20:433–438
257. Crino PB, Ullman MD, Vogt BA, Bird ED, Volicer L (1989) Brain gangliosides in dementia of the Alzheimer type. Arch Neurol 46:398–401
258. Katsel P, Li C, Haroutunian V (2007) Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and Alzheimer’s disease: a shift toward ceramide accumulation at the earliest recognizable stages of Alzheimer’s disease? Neurochem Res 32:845–856
259. Molander-Melin M, Blennow K, Bogdanovic N, Dellheden B, Mansson JE, Fredman P (2005) 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 92:171–182
260. Rushworth JV, Hooper NM (2010) Lipid rafts: linking Alzheimer’s amyloid-beta production, aggregation, and toxicity at neuronal membranes. Int J Alzheimers Dis 2011:603052
261. Hicks DA, Nalivaeva NN, Turner AJ (2012) Lipid rafts and Alzheimer’s disease: protein–lipid interactions and perturbation of signaling. Front Physiol 3:189
262. Costanzo M, Zurzolo C (2013) The cell biology of prion-like spread of protein aggregates: mechanisms and implication in neurodegeneration. Biochem J 452:1–17
263. Fantini J, Yahi N (2013) The driving force of alpha-synuclein insertion and amyloid channel formation in the plasma membrane of neural cells: key role of ganglioside- and cholesterol-binding domains. Adv Exp Med Biol 991:15–26
264. Teich AF, Arancio O (2012) Is the amyloid hypothesis of Alzheimer’s disease therapeutically relevant? Biochem J 446:165–177
265. Shvadchak VV, Falomir-Lockhart LJ, Yushchenko DA, Jovin TM (2011) Specificity and kinetics of alpha-synuclein binding to model membranes determined with fluorescent excited state intramolecular proton transfer (ESIPT) probe. J Biol Chem 286:13023–13032
266. Shvadchak VV, Yushchenko DA, Pievo R, Jovin TM (2011) The mode of alpha-synuclein binding to membranes depends on lipid composition and lipid to protein ratio. FEBS Lett 585:3513–3519
267. Leftin A, Job C, Beyer K, Brown MF (2013) Solid-state (1)(3)C NMR reveals annealing of raft-like membranes containing cholesterol by the intrinsically disordered protein alpha-Synuclein. J Mol Biol 425:2973–2987
268. Manna M, Mukhopadhyay C (2013) Binding, conformational transition and dimerization of amyloid-beta peptide on GM1-containing ternary membrane: insights from molecular dynamics simulation. PLoS ONE 8:e71308
269. Beel AJ, Sakakura M, Barrett PJ, Sanders CR (2010) Direct binding of cholesterol to the amyloid precursor protein: an important interaction in lipid-Alzheimer’s disease relationships? Biochim Biophys Acta 1801:975–982
270. Fantini J, Yahi N, Garmy N (2013) Cholesterol accelerates the binding of Alzheimer’s beta-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation. Front Physiol 4:120
271. Song Y, Hustedt EJ, Brandon S, Sanders CR (2013) Competition between homodimerization and cholesterol binding to the C99 domain of the amyloid precursor protein. Biochemistry 52:5051–5064
272. Barrett PJ, Song Y, Van Horn WD, Hustedt EJ, Schafer JM, Hadziselimovic A, Beel AJ, Sanders CR (2012) The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science 336:1168–1171
273. Minami SS, Hoe HS, Rebeck GW (2011) Fyn kinase regulates the association between amyloid precursor protein and Dab1 by promoting their localization to detergent-resistant membranes. J Neurochem 118:879–890
274. Nalivaeva NN, Turner AJ (2013) The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett 587:2046–2054
275. Muller UC, Zheng H (2012) Physiological functions of APP family proteins. Cold Spring Harb Perspect Med 2:a006288
276. Brouillet E, Trembleau A, Galanaud D, Volovitch M, Bouillot C, Valenza C, Prochiantz A, Allinquant B (1999) The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. J Neurosci 19:1717–1727
277. Ashall F, Goate AM (1994) Role of the beta-amyloid precursor protein in Alzheimer’s disease. Trends Biochem Sci 19:42–46
278. Hartmann T, Kuchenbecker J, Grimm MO (2007) Alzheimer’s disease: the lipid connection. J Neurochem 103(Suppl 1):159–170
279. Grimm MO, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T (2005) Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol 7:1118–1123
280. Grimm MO, Kuchenbecker J, Rothhaar TL, Grosgen S, Hundsdorfer B, Burg VK, Friess P, Muller U, Grimm HS, Riemenschneider M, Hartmann T (2011) Plasmalogen synthesis is regulated via alkyl-dihydroxyacetonephosphate-synthase by amyloid precursor protein processing and is affected in Alzheimer’s disease. J Neurochem 116:916–925
281. Grimm MO, Grosgen S, Rothhaar TL, Burg VK, Hundsdorfer B, Haupenthal VJ, Friess P, Muller U, Fassbender K, Riemenschneider M, Grimm HS, Hartmann T (2011) Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer’s Disease. Int J Alzheimers Dis 2011:695413
282. Yanagisawa K, Odaka A, Suzuki N, Ihara Y (1995) GM1 ganglioside-bound amyloid beta-protein (A beta): a possible form of preamyloid in Alzheimer’s disease. Nat Med 1:1062–1066
283. Kakio A, Nishimoto SI, Yanagisawa K, Kozutsumi Y, Matsuzaki K (2001) Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid. J Biol Chem 276:24985–24990
284. Kim SI, Yi JS, Ko YG (2006) Amyloid beta oligomerization is induced by brain lipid rafts. J Cell Biochem 99:878–889
285. Yanagisawa K, Fantini J, Chakrabartty A, Eckert A (2011) Abeta behavior on neuronal membranes: aggregation and toxicities. Int J Alzheimers Dis 2011:286536
286. Rushworth JV, Griffiths HH, Watt NT, Hooper NM (2013) Prion protein-mediated toxicity of amyloid-beta oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem 288:8935–8951
287. Blom K, Emmelot-Vonk MH, Koek HD (2013) The influence of vascular risk factors on cognitive decline in patients with dementia: a systematic review. Maturitas 76:113–117
288. Wood WG, Igbavboa U, Eckert GP, Johnson-Anuna LN, Muller WE (2005) Is hypercholesterolemia a risk factor for Alzheimer’s disease? Mol Neurobiol 31:185–192
289. Wood WG, Eckert GP, Igbavboa U, Muller WE (2010) Statins and neuroprotection: a prescription to move the field forward. Ann N Y Acad Sci 1199:69–76