title: Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases.
abstract: Alzheimer, Parkinson and other neurodegenerative diseases involve a series of brain proteins, referred to as 'amyloidogenic proteins', with exceptional conformational plasticity and a high propensity for self-aggregation. Although the mechanisms by which amyloidogenic proteins kill neural cells are not fully understood, a common feature is the concentration of unstructured amyloidogenic monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a series of lipid-dependent conformational changes, leading to the formation of oligomers of varying toxicity rich in beta-sheet structures (annular pores, amyloid fibrils) or in alpha-helix structures (transmembrane channels). Condensed membrane nano- or microdomains formed by sphingolipids and cholesterol are privileged sites for the binding and oligomerisation of amyloidogenic proteins. By controlling the balance between unstructured monomers and alpha or beta conformers (the chaperone effect), sphingolipids can either inhibit or stimulate the oligomerisation of amyloidogenic proteins. Cholesterol has a dual role: regulation of protein-sphingolipid interactions through a fine tuning of sphingolipid conformation (indirect effect), and facilitation of pore (or channel) formation through direct binding to amyloidogenic proteins. Deciphering this complex network of molecular interactions in the context of age- and disease-related evolution of brain lipid expression will help understanding of how amyloidogenic proteins induce neural toxicity and will stimulate the development of innovative therapies for neurodegenerative diseases.
authors.affiliation: Laboratoire des Interactions Moléculaires et Systèmes Membranaires, Marseille, France. jacques.fantini@univ-cezanne.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.forename: Nouara
authors.initials: N
authors.lastname: Yahi
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D000682:Amyloid; D013107:Sphingolipids; D002784:Cholesterol
references.citation: Mol Biol Cell. 2004 Sep;15(9):4031-42
references.pmid: 15229281
references.citation: Neurology. 2000;54(11 Suppl 5):S10-5
references.pmid: 10854355
references.citation: Biochem Biophys Res Commun. 2008 Jun 6;370(3):525-9
references.pmid: 18395518
references.citation: Colloids Surf B Biointerfaces. 2009 Dec 1;74(2):436-56
references.pmid: 19726167
references.citation: J Neurol Sci. 2009 Aug 15;283(1-2):230-4
references.pmid: 19321181
references.citation: Eur Biophys J. 2008 Mar;37(3):247-55
references.pmid: 18030461
references.citation: Exp Neurol. 2000 Jul;164(1):121-9
references.pmid: 10877922
references.citation: J Am Chem Soc. 2008 Oct 1;130(39):12856-7
references.pmid: 18774805
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19666-71
references.pmid: 19066219
references.citation: J Biol Chem. 1998 Apr 3;273(14):7967-71
references.pmid: 9525894
references.citation: Biochim Biophys Acta. 2009 Nov;1788(11):2345-61
references.pmid: 19733149
references.citation: Curr Med Chem. 2007;14(27):2911-7
references.pmid: 18045136
references.citation: J Mol Biol. 2007 Aug 24;371(4):924-33
references.pmid: 17597153
references.citation: J Mol Biol. 2009 Oct 30;393(3):765-75
references.pmid: 19720065
references.citation: Biochemistry. 2007 Feb 20;46(7):1868-77
references.pmid: 17253773
references.citation: Biochim Biophys Acta. 2010 Jun;1798(6):1090-9
references.pmid: 20226163
references.citation: Biochem J. 2006 Aug 1;397(3):483-90
references.pmid: 16626304
references.citation: FEBS J. 2007 Apr;274(7):1862-77
references.pmid: 17381514
references.citation: Mol Cell Biochem. 1994 Nov 23;140(2):119-25
references.pmid: 7898484
references.citation: Cell Mol Life Sci. 2003 Jun;60(6):1027-32
references.pmid: 12866532
references.citation: Biochemistry. 2010 Feb 9;49(5):862-71
references.pmid: 20041693
references.citation: Science. 1991 Jul 19;253(5017):320-3
references.pmid: 1857969
references.citation: Neurobiol Aging. 2009 Apr;30(4):591-9
references.pmid: 17888544
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3348-53
references.pmid: 19204293
references.citation: J Biol Chem. 1999 Jul 23;274(30):20763-71
references.pmid: 10409615
references.citation: Acta Neurol Scand. 2002 Jul;106(1):54-7
references.pmid: 12067330
references.citation: BMC Genomics. 2009 Jul 07;10 Suppl 1:S7
references.pmid: 19594884
references.citation: J Neurochem. 2007 May;101(4):1072-84
references.pmid: 17437537
references.citation: Chem Phys Lipids. 1990 Jan;52(1):1-10
references.pmid: 2306786
references.citation: Biochemistry. 1998 Aug 4;37(31):11064-77
references.pmid: 9693002
references.citation: J Neurochem. 2006 Aug;98(4):1032-45
references.pmid: 16895578
references.citation: Arch Neurol. 2005 Jul;62(7):1047-51
references.pmid: 16009757
references.citation: Micron. 2002;33(7-8):609-26
references.pmid: 12475558
references.citation: Biochim Biophys Acta. 2007 Aug;1768(8):1935-42
references.pmid: 17382287
references.citation: J Neurochem. 1994 Mar;62(3):1039-47
references.pmid: 8113790
references.citation: J Virol. 1999 Jun;73(6):5244-8
references.pmid: 10233996
references.citation: EMBO J. 2002 Apr 15;21(8):1899-908
references.pmid: 11953309
references.citation: FASEB J. 2002 Jan;16(1):77-83
references.pmid: 11772939
references.citation: J Neurochem. 2009 Dec;111(6):1275-308
references.pmid: 20050287
references.citation: Biochemistry. 2003 Jan 28;42(3):829-37
references.pmid: 12534296
references.citation: PLoS One. 2010 Feb 05;5(2):e9079
references.pmid: 20140095
references.citation: Biochemistry. 2007 Dec 18;46(50):14369-79
references.pmid: 18031063
references.citation: J Biol Chem. 2005 Mar 11;280(10):9595-603
references.pmid: 15615727
references.citation: Nat Med. 1995 Oct;1(10):1062-6
references.pmid: 7489364
references.citation: Science. 1992 Apr 10;256(5054):184-5
references.pmid: 1566067
references.citation: J Lipid Res. 2008 Jun;49(6):1157-75
references.pmid: 18334715
references.citation: Glycoconj J. 2009 Nov;26(8):999-1006
references.pmid: 19052862
references.citation: Angew Chem Int Ed Engl. 2010 Aug 2;49(33):5628-54
references.pmid: 20623810
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83
references.pmid: 9811807
references.citation: Mol Cell Neurosci. 2010 Jan;43(1):33-42
references.pmid: 19660552
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71
references.pmid: 8380642
references.citation: Biochem J. 2004 Sep 15;382(Pt 3):987-94
references.pmid: 15202933
references.citation: Expert Rev Mol Med. 2002 Dec 20;4(27):1-22
references.pmid: 14987385
references.citation: FASEB J. 2002 Oct;16(12):1526-36
references.pmid: 12374775
references.citation: J Virol. 1992 Aug;66(8):4848-54
references.pmid: 1378511
references.citation: J Biol Chem. 2008 Oct 31;283(44):29639-43
references.pmid: 18723507
references.citation: J Mol Biol. 1999 Oct 22;293(2):321-31
references.pmid: 10550212
references.citation: FEBS J. 2006 Dec;273(24):5724-35
references.pmid: 17212787
references.citation: Micron. 2008 Dec;39(8):1192-6
references.pmid: 18586500
references.citation: J Mol Biol. 2001 Aug 24;311(4):723-34
references.pmid: 11518526
references.citation: J Biol Chem. 2001 Sep 7;276(36):33561-8
references.pmid: 11438533
references.citation: J Neurochem. 2008 Aug;106(3):1459-70
references.pmid: 18498440
references.citation: Biochem J. 1995 Oct 1;311 ( Pt 1):1-16
references.pmid: 7575439
references.citation: FASEB J. 2006 Jun;20(8):1248-50
references.pmid: 16636105
references.citation: Neurobiol Aging. 2010 Nov;31(11):1843-53
references.pmid: 19036474
references.citation: Biochemistry. 2008 Dec 23;47(51):13604-9
references.pmid: 19049426
references.citation: Science. 2007 Nov 23;318(5854):1258-65
references.pmid: 17962520
references.citation: Biochim Biophys Acta. 1990 Oct 8;1031(3):277-89
references.pmid: 2171656
references.citation: J Biol Chem. 2005 Sep 9;280(36):31664-72
references.pmid: 16020543
references.citation: J Neurosci. 2002 Oct 15;22(20):8797-807
references.pmid: 12388586
references.citation: Q Rev Biophys. 2006 May;39(2):167-201
references.pmid: 16978447
references.citation: Biotechnol Bioeng. 2008 Mar 1;99(4):753-63
references.pmid: 17994591
references.citation: Biochim Biophys Acta. 2010 Apr;1802(4):406-15
references.pmid: 20060899
references.citation: FEBS Lett. 2004 Feb 27;560(1-3):14-8
references.pmid: 14987990
references.citation: J Biol Chem. 2002 Mar 29;277(13):11292-6
references.pmid: 11792705
references.citation: Cell Death Differ. 2008 Dec;15(12):1824-37
references.pmid: 18670435
references.citation: J Lipid Res. 2003 Nov;44(11):2019-29
references.pmid: 12951356
references.citation: Biochim Biophys Acta. 2006 Aug;1761(8):927-46
references.pmid: 16901751
references.citation: Peptides. 2001 Jul;22(7):1099-106
references.pmid: 11445240
references.citation: Biopolymers. 2003 May;69(1):29-41
references.pmid: 12717720
references.citation: Cancer Lett. 2009 Jun 18;278(2):164-173
references.pmid: 19216024
references.citation: Biochemistry. 2004 Aug 17;43(32):10302-7
references.pmid: 15301528
references.citation: Biochemistry. 1996 Dec 10;35(49):15663-71
references.pmid: 8961929
references.citation: Curr Opin Struct Biol. 1998 Aug;8(4):525-33
references.pmid: 9729746
references.citation: FEBS Lett. 2010 May 3;584(9):1748-59
references.pmid: 20006608
references.citation: J Biol Chem. 2001 Apr 20;276(16):12945-50
references.pmid: 11134035
references.citation: J Lipid Res. 2008 Oct;49(10):2268-75
references.pmid: 18603643
references.citation: Neurology. 2008 May 20;70(21):1972-9
references.pmid: 18401018
references.citation: Nat Genet. 2004 Nov;36(11):1225-9
references.pmid: 15502825
references.citation: J Biol Chem. 2000 Nov 3;275(44):34328-34
references.pmid: 10915790
references.citation: FEMS Microbiol Lett. 2004 Sep 15;238(2):281-9
references.pmid: 15358412
references.citation: Pediatr Res. 2004 Sep;56(3):449-63
references.pmid: 15240864
references.citation: J Neurochem. 2006 May;97(4):1071-7
references.pmid: 16606366
references.citation: J Mol Biol. 2008 Oct 17;382(4):1066-74
references.pmid: 18692507
references.citation: Nat Cell Biol. 2005 Nov;7(11):1118-23
references.pmid: 16227967
references.citation: Science. 2003 Apr 18;300(5618):486-9
references.pmid: 12702875
references.citation: Neuroreport. 2009 Aug 5;20(12):1043-6
references.pmid: 19590389
references.citation: Nat Chem Biol. 2006 May;2(5):249-53
references.pmid: 16565714
references.citation: J Mol Biol. 2002 Feb 1;315(5):1241-56
references.pmid: 11827491
references.citation: Biochem Biophys Res Commun. 2003 Apr 4;303(2):514-8
references.pmid: 12659848
references.citation: J Biomol Struct Dyn. 2003 Oct;21(2):211-34
references.pmid: 12956606
references.citation: J Mol Biol. 2008 Feb 1;375(5):1394-404
references.pmid: 18082181
references.citation: J Neurochem. 2008 Jun;105(5):1656-67
references.pmid: 18248604
references.citation: Phys Chem Chem Phys. 2008 May 21;10(19):2792-800
references.pmid: 18464996
references.citation: Neurochem Int. 1992 Apr;20(3):433-8
references.pmid: 1304338
references.citation: J Cell Biol. 2010 Feb 22;188(4):581-94
references.pmid: 20176925
references.citation: J Biol Chem. 2004 Nov 5;279(45):46363-6
references.pmid: 15385542
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S440-5
references.pmid: 18845618
references.citation: Biochim Biophys Acta. 2007 Aug;1768(8):1862-85
references.pmid: 17493579
references.citation: J Biol Chem. 2005 Jul 29;280(30):28110-7
references.pmid: 15923191
references.citation: J Neurochem. 2005 Jan;92(1):171-82
references.pmid: 15606906
references.citation: J Mol Biol. 2007 Aug 10;371(2):481-9
references.pmid: 17582434
references.citation: J Biomed Biotechnol. 2010;2010:568068
references.pmid: 20011072
references.citation: Biochim Biophys Acta. 2010 Aug;1801(8):975-82
references.pmid: 20304095
references.citation: FEBS Lett. 1997 Feb 3;402(2-3):95-8
references.pmid: 9037173
references.citation: Biochim Biophys Acta. 1987 Jun 24;906(2):137-60
references.pmid: 3036228
references.citation: Science. 2010 Jan 1;327(5961):46-50
references.pmid: 20044567
references.citation: Cell Mol Life Sci. 2005 Oct;62(19-20):2283-94
references.pmid: 16158191
references.citation: EMBO Rep. 2004 Aug;5(8):777-82
references.pmid: 15289826
references.citation: Subcell Biochem. 2005;38:179-202
references.pmid: 15709479
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10427-32
references.pmid: 16020533
references.citation: Nat Chem Biol. 2008 Apr;4(4):229-30
references.pmid: 18347590
references.citation: Virology. 1994 Jun;201(2):206-14
references.pmid: 8184533
references.citation: J Lipid Res. 2008 May;49(5):1077-89
references.pmid: 18263852
references.citation: J Mol Biol. 2010 Mar 19;397(1):202-18
references.pmid: 20114052
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3563-8
references.pmid: 11891310
references.citation: Adv Drug Deliv Rev. 2004 Apr 19;56(6):779-94
references.pmid: 15063589
references.citation: FEBS J. 2006 Apr;273(7):1389-402
references.pmid: 16689927
references.citation: Biochemistry. 2003 Nov 11;42(44):12919-26
references.pmid: 14596606
references.citation: Biochim Biophys Acta. 2010 Aug;1801(8):868-77
references.pmid: 20117237
references.citation: J Lipid Res. 2002 Oct;43(10):1670-9
references.pmid: 12364551
references.citation: Neurobiol Aging. 2007 Dec;28(12):1863-72
references.pmid: 17007963
references.citation: Nat Struct Biol. 2001 Sep;8(9):770-4
references.pmid: 11524679
references.citation: Biochemistry. 2006 Sep 12;45(36):10957-62
references.pmid: 16953581
references.citation: J Neurochem. 2007 Oct;103(1):17-37
references.pmid: 17623039
references.citation: J Mol Biol. 2009 Jun 26;389(5):907-20
references.pmid: 19427320
references.citation: Nature. 1997 Jun 5;387(6633):569-72
references.pmid: 9177342
references.citation: Nature. 2002 Jul 18;418(6895):291
references.pmid: 12124613
references.citation: Hum Genet. 1998 Jan;102(1):57-62
references.pmid: 9490299
references.citation: Aging Clin Exp Res. 2009 Dec;21(6):386-406
references.pmid: 20154508
references.citation: J Neurochem. 1994 Nov;63(5):1802-11
references.pmid: 7931336
references.citation: Biochemistry. 2002 Jun 11;41(23):7385-90
references.pmid: 12044171
references.citation: J Biol Chem. 1998 Feb 20;273(8):4506-15
references.pmid: 9468505
references.citation: Exp Neurol. 2010 Feb;221(2):267-74
references.pmid: 19944097
references.citation: J Neurochem. 2007 Nov;103 Suppl 1:159-70
references.pmid: 17986151
references.citation: Neurobiol Aging. 2010 Mar;31(3):398-408
references.pmid: 18547682