title: Polyglutamine neurodegeneration: protein misfolding revisited.
abstract: Polyglutamine diseases are a major cause of neurodegeneration worldwide. Recent studies highlight the importance of protein quality control mechanisms in regulating polyglutamine-induced toxicity. Here we discuss a model of disease pathogenesis that integrates current understanding of the role of protein folding in polyglutamine disease with emerging evidence that alterations in native protein interactions contribute to toxicity. We also incorporate new findings on other age-related neurodegenerative diseases in an effort to explain how protein aggregation and normal aging processes might be involved in polyglutamine disease pathogenesis.
authors.affiliation: Program in Neuroscience and Medical Scientist Training Program, University of Iowa, 2206 MERF, Iowa City, IA 52242, USA.
authors.forename: Aislinn J
authors.initials: AJ
authors.lastname: Williams
authors.forename: Henry L
authors.initials: HL
authors.lastname: Paulson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D006801:Humans; D008954:Models, Biological; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D017510:Protein Folding
chemical_list: D010455:Peptides; C097188:polyglutamine
references.citation: PLoS One. 2006 Dec 27;1:e111
references.pmid: 17205115
references.citation: Nat Med. 2005 Oct;11(10):1088-95
references.pmid: 16155577
references.citation: J Neurochem. 2008 Feb;104(3):846-58
references.pmid: 17986219
references.citation: Nature. 2008 Apr 10;452(7188):713-8
references.pmid: 18337722
references.citation: Science. 2006 Sep 15;313(5793):1604-10
references.pmid: 16902091
references.citation: Hum Mol Genet. 2007 Apr 1;16(7):848-64
references.pmid: 17317785
references.citation: PLoS Genet. 2007 Oct;3(10):1950-64
references.pmid: 17953484
references.citation: Neuron. 1999 Dec;24(4):879-92
references.pmid: 10624951
references.citation: Nat Rev Neurosci. 2005 Jan;6(1):11-22
references.pmid: 15611723
references.citation: Biophys J. 2006 Jun 15;90(12):4574-84
references.pmid: 16565057
references.citation: Mol Cell Biol. 2003 May;23(9):3141-51
references.pmid: 12697815
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10417-22
references.pmid: 12122205
references.citation: Nature. 2007 Aug 9;448(7154):704-8
references.pmid: 17687326
references.citation: Mol Cell. 2006 Sep 15;23(6):887-97
references.pmid: 16973440
references.citation: J Mol Biol. 2007 Apr 27;368(2):595-605
references.pmid: 17362987
references.citation: Cell. 1998 Oct 2;95(1):55-66
references.pmid: 9778247
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11884-9
references.pmid: 12186976
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5868-73
references.pmid: 18398004
references.citation: J Neurosci. 2007 Jan 24;27(4):868-80
references.pmid: 17251428
references.citation: Nat Struct Mol Biol. 2007 Apr;14(4):332-40
references.pmid: 17369839
references.citation: Hum Mol Genet. 2008 Feb 1;17(3):345-56
references.pmid: 17947294
references.citation: J Neurosci. 2005 Oct 19;25(42):9773-81
references.pmid: 16237181
references.citation: Nat Cell Biol. 2006 Oct;8(10):1155-62
references.pmid: 16980959
references.citation: Nature. 2008 Jun 19;453(7198):1107-11
references.pmid: 18449188
references.citation: J Neurosci. 2005 Oct 5;25(40):9152-61
references.pmid: 16207874
references.citation: Nature. 2007 Jun 14;447(7146):859-63
references.pmid: 17568747
references.citation: Nat Rev Genet. 2005 Oct;6(10):743-55
references.pmid: 16205714
references.citation: J Neurochem. 2007 Jun;101(5):1172-84
references.pmid: 17286590
references.citation: EMBO J. 2004 Feb 11;23(3):659-69
references.pmid: 14749733
references.citation: Biochemistry. 2002 Jun 11;41(23):7391-9
references.pmid: 12044172
references.citation: Nature. 2004 Oct 14;431(7010):805-10
references.pmid: 15483602
references.citation: Mol Cell Neurosci. 2007 Jan;34(1):69-79
references.pmid: 17127076
references.citation: J Neurosci. 2006 Jul 19;26(29):7597-606
references.pmid: 16855087
references.citation: Nat Struct Mol Biol. 2007 May;14(5):381-7
references.pmid: 17450152
references.citation: Science. 2008 Feb 15;319(5865):916-9
references.pmid: 18276881
references.citation: Nature. 2006 Mar 16;440(7082):352-7
references.pmid: 16541076
references.citation: BMC Genomics. 2007 May 22;8:126
references.pmid: 17519034
references.citation: PLoS Genet. 2007 May 11;3(5):e82
references.pmid: 17500595
references.citation: Annu Rev Neurosci. 2000;23:217-47
references.pmid: 10845064
references.citation: J Biol Chem. 2007 Feb 2;282(5):3157-64
references.pmid: 17121819
references.citation: Science. 2006 Mar 10;311(5766):1471-4
references.pmid: 16469881
references.citation: Brain Pathol. 2006 Jul;16(3):218-27
references.pmid: 16911479
references.citation: J Biol Chem. 2007 Aug 17;282(33):23818-28
references.pmid: 17548355
references.citation: J Mol Biol. 2007 Aug 3;371(1):235-44
references.pmid: 17560603
references.citation: J Biol Chem. 2003 Jun 13;278(24):22044-55
references.pmid: 12676955
references.citation: J Neurosci. 2007 May 9;27(19):5115-26
references.pmid: 17494697
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6403-8
references.pmid: 15084750
references.citation: Mol Cell. 2004 Jul 2;15(1):95-105
references.pmid: 15225551
references.citation: Hum Mol Genet. 2008 Feb 1;17(3):376-90
references.pmid: 17984172
references.citation: J Biol Chem. 2008 Mar 21;283(12):7648-56
references.pmid: 18201976
references.citation: J Biol Chem. 2005 Mar 25;280(12):11635-40
references.pmid: 15664989
references.citation: Nat Cell Biol. 2006 Oct;8(10):1163-70
references.pmid: 16980958
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11402-7
references.pmid: 16076956
references.citation: Science. 2003 May 16;300(5622):1142-5
references.pmid: 12750521
references.citation: Cell. 2006 Dec 29;127(7):1335-47
references.pmid: 17190598
references.citation: Nat Neurosci. 2007 Dec;10(12):1519-28
references.pmid: 17994014
references.citation: J Neurosci. 2006 Jun 28;26(26):6985-96
references.pmid: 16807328
references.citation: J Biol Chem. 2005 Jun 24;280(25):23727-34
references.pmid: 15845543
references.citation: J Biol Chem. 2006 Sep 8;281(36):26714-24
references.pmid: 16831871