title: Chaperone networks: tipping the balance in protein folding diseases.
abstract: Adult-onset neurodegeneration and other protein conformational diseases are associated with the appearance, persistence, and accumulation of misfolded and aggregation-prone proteins. To protect the proteome from long-term damage, the cell expresses a highly integrated protein homeostasis (proteostasis) machinery to ensure that proteins are properly expressed, folded, and cleared, and to recognize damaged proteins. Molecular chaperones have a central role in proteostasis as they have been shown to be essential to prevent the accumulation of alternate folded proteotoxic states as occurs in protein conformation diseases exemplified by neurodegeneration. Studies using invertebrate models expressing proteins associated with Huntington's disease, Alzheimer's disease, ALS, and Parkinson's disease have provided insights into the genetic networks and stress signaling pathways that regulate the proteostasis machinery to prevent cellular dysfunction, tissue pathology, and organismal failure. These events appear to be further amplified by aging and provide evidence that age-related failures in proteostasis may be a common element in many diseases.
authors.affiliation: Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Voisine
authors.forename: Jesper Søndergaard
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Richard I
authors.initials: RI
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics*; D011487:Protein Conformation; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones
references.citation: Genes Dev. 2001 Apr 15;15(8):925-32
references.pmid: 11316786
references.citation: Mol Cell Biol. 1999 Jun;19(6):4535-45
references.pmid: 10330192
references.citation: Mech Ageing Dev. 2005 Sep;126(9):913-22
references.pmid: 15885745
references.citation: Nature. 1995 Nov 23;378(6555):403-6
references.pmid: 7477379
references.citation: Cell. 1998 Feb 6;92(3):351-66
references.pmid: 9476895
references.citation: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4651-5
references.pmid: 7753858
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9980-5
references.pmid: 12872001
references.citation: Aging Cell. 2009 Sep;8(5):524-41
references.pmid: 19575768
references.citation: Nature. 1999 Aug 12;400(6745):693-6
references.pmid: 10458167
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10417-22
references.pmid: 12122205
references.citation: Genes Dev. 1998 Mar 1;12(5):654-66
references.pmid: 9499401
references.citation: Nat Genet. 1999 Dec;23(4):425-8
references.pmid: 10581028
references.citation: Annu Rev Biochem. 2009;78:959-91
references.pmid: 19298183
references.citation: J Biol Chem. 2008 Jan 11;283(2):784-91
references.pmid: 17993648
references.citation: Mol Cell Biol. 1994 Nov;14(11):7592-603
references.pmid: 7935474
references.citation: Science. 2004 Mar 26;303(5666):2011-5
references.pmid: 14976264
references.citation: Aging Cell. 2009 Jun;8(3):258-69
references.pmid: 19627265
references.citation: Genes Dev. 1997 Jul 15;11(14):1775-85
references.pmid: 9242486
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9439-44
references.pmid: 12089340
references.citation: Cell. 1991 May 3;65(3):363-6
references.pmid: 2018972
references.citation: J Biol Chem. 1994 Dec 23;269(51):32272-8
references.pmid: 7798227
references.citation: Nat Cell Biol. 2001 Jan;3(1):100-5
references.pmid: 11146634
references.citation: Cell. 2009 Dec 11;139(6):1157-69
references.pmid: 20005808
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):179-84
references.pmid: 9874792
references.citation: J Struct Biol. 2001 Aug;135(2):84-93
references.pmid: 11580258
references.citation: Mol Cell Biol. 1997 Apr;17(4):2107-15
references.pmid: 9121459
references.citation: Mol Cell Biol. 2006 Feb;26(3):955-64
references.pmid: 16428449
references.citation: Ageing Res Rev. 2007 Aug;6(2):128-40
references.pmid: 17512264
references.citation: Nature. 1997 Nov 6;390(6655):30
references.pmid: 9363888
references.citation: Cell. 1998 Jun 12;93(6):939-49
references.pmid: 9635424
references.citation: Science. 2009 Feb 20;323(5917):1063-6
references.pmid: 19229036
references.citation: Science. 2002 Mar 8;295(5561):1852-8
references.pmid: 11884745
references.citation: FASEB J. 2001 May;15(7):1118-31
references.pmid: 11344080
references.citation: Annu Rev Genet. 1988;22:631-77
references.pmid: 2853609
references.citation: Essays Biochem. 1997;32:17-29
references.pmid: 9493008
references.citation: Mol Cell Biol. 1988 Nov;8(11):4736-44
references.pmid: 3211126
references.citation: FEBS Lett. 2002 Apr 10;516(1-3):53-7
references.pmid: 11959102
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):5750-5
references.pmid: 10811890
references.citation: EMBO J. 2003 Oct 1;22(19):5230-40
references.pmid: 14517260
references.citation: Nat Cell Biol. 2001 Jan;3(1):93-6
references.pmid: 11146632
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9368-72
references.pmid: 7568134
references.citation: Nature. 1996 Jun 13;381(6583):571-9
references.pmid: 8637592
references.citation: Biochemistry. 2003 May 6;42(17):4937-44
references.pmid: 12718535
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13318-23
references.pmid: 11687635
references.citation: Cell. 1999 Jun 11;97(6):755-65
references.pmid: 10380927
references.citation: Biochim Biophys Acta. 2004 Nov 29;1695(1-3):171-88
references.pmid: 15571814
references.citation: FASEB J. 1999 Aug;13(11):1385-93
references.pmid: 10428762
references.citation: Science. 2001 Feb 23;291(5508):1553-7
references.pmid: 11222862
references.citation: Nature. 2003 Jan 9;421(6919):182-7
references.pmid: 12483226
references.citation: Nature. 2000 Feb 17;403(6771):795-800
references.pmid: 10693811
references.citation: Science. 1973 Jul 20;181(4096):223-30
references.pmid: 4124164
references.citation: J Neurosci. 2006 Jul 19;26(29):7597-606
references.pmid: 16855087
references.citation: Mol Cell. 2003 Jul;12(1):87-100
references.pmid: 12887895
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: J Biol Chem. 2008 Jan 4;283(1):194-201
references.pmid: 17951251
references.citation: Science. 2008 Feb 15;319(5865):916-9
references.pmid: 18276881
references.citation: PLoS Genet. 2008 Mar 21;4(3):e1000027
references.pmid: 18369446
references.citation: Genetics. 2002 Jul;161(3):1101-12
references.pmid: 12136014
references.citation: Science. 1996 Dec 6;274(5293):1713-5
references.pmid: 8939862
references.citation: Genetics. 1995 Dec;141(4):1399-406
references.pmid: 8601482
references.citation: Annu Rev Biochem. 2001;70:603-47
references.pmid: 11395418
references.citation: Science. 1997 Nov 14;278(5341):1319-22
references.pmid: 9360933
references.citation: Mol Biol Cell. 2004 Feb;15(2):657-64
references.pmid: 14668486
references.citation: Science. 2003 Jun 20;300(5627):1921
references.pmid: 12817143
references.citation: Science. 2006 Mar 10;311(5766):1471-4
references.pmid: 16469881
references.citation: EMBO J. 2009 Dec 2;28(23):3758-70
references.pmid: 19875982
references.citation: Hum Mol Genet. 2000 Nov 22;9(19):2811-20
references.pmid: 11092757
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14914-9
references.pmid: 19706382
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16407-11
references.pmid: 12149445
references.citation: Science. 2006 Sep 15;313(5793):1604-10
references.pmid: 16902091
references.citation: Science. 1995 Mar 17;267(5204):1619-20
references.pmid: 7886447
references.citation: Mech Ageing Dev. 2009 Jun;130(6):357-69
references.pmid: 19428455
references.citation: Cell. 1994 Jul 1;77(7):1027-36
references.pmid: 8020093
references.citation: Science. 1993 Mar 5;259(5100):1409-10
references.pmid: 8451637
references.citation: Aging Cell. 2006 Oct;5(5):413-22
references.pmid: 16939484
references.citation: Biochem J. 2005 Dec 15;392(Pt 3):573-81
references.pmid: 16053447
references.citation: PLoS Genet. 2007 Oct;3(10):1950-64
references.pmid: 17953484
references.citation: Mol Cell Biol. 1998 Apr;18(4):2023-8
references.pmid: 9528774
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7540-4
references.pmid: 7638227
references.citation: Aging Cell. 2003 Apr;2(2):131-9
references.pmid: 12882326
references.citation: Ann N Y Acad Sci. 2005 Dec;1066:181-221
references.pmid: 16533927
references.citation: Nature. 1992 Jan 2;355(6355):33-45
references.pmid: 1731198
references.citation: J Biol Chem. 2006 Jan 6;281(1):334-40
references.pmid: 16260788
references.citation: Genes Dev. 1996 Nov 1;10(21):2782-93
references.pmid: 8946918
references.citation: Nat Genet. 2005 Aug;37(8):894-8
references.pmid: 16041374
references.citation: Nature. 2002 Apr 4;416(6880):507-11
references.pmid: 11932737
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13732-7
references.pmid: 10570141
references.citation: Genes Dev. 1998 Dec 15;12(24):3788-96
references.pmid: 9869631
references.citation: EMBO J. 1999 Jan 4;18(1):75-84
references.pmid: 9878052
references.citation: Neuron. 2002 Aug 29;35(5):819-22
references.pmid: 12372277
references.citation: Aging Cell. 2008 Jun;7(3):394-404
references.pmid: 18331616
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6403-8
references.pmid: 15084750
references.citation: Aging Cell. 2009 Apr;8(2):113-27
references.pmid: 19239417
references.citation: Nature. 2001 Mar 8;410(6825):227-30
references.pmid: 11242085
references.citation: EMBO J. 1995 May 15;14(10):2281-92
references.pmid: 7774586
references.citation: Science. 1997 Aug 15;277(5328):942-6
references.pmid: 9252323
references.citation: PLoS Genet. 2009 Mar;5(3):e1000399
references.pmid: 19266020
references.citation: EMBO J. 1998 Dec 1;17(23):6871-8
references.pmid: 9843493
references.citation: Arch Neurol. 2008 Feb;65(2):184-9
references.pmid: 18268186
references.citation: Science. 2003 May 16;300(5622):1142-5
references.pmid: 12750521
references.citation: Cell. 1998 Oct 16;95(2):199-210
references.pmid: 9790527
references.citation: J Gerontol A Biol Sci Med Sci. 2001 Jul;56(7):B281-7
references.pmid: 11445592
references.citation: Endocr Rev. 1997 Jun;18(3):306-60
references.pmid: 9183567
references.citation: Science. 1996 Aug 2;273(5275):622-6
references.pmid: 8662547
references.citation: Nat Cell Biol. 2001 Oct;3(10):E237-41
references.pmid: 11584289
references.citation: Cell. 2008 Mar 21;132(6):1025-38
references.pmid: 18358814
references.citation: EMBO J. 1999 Jan 4;18(1):85-95
references.pmid: 9878053
references.citation: Hum Mol Genet. 2006 May 1;15(9):1483-96
references.pmid: 16600994
references.citation: PLoS Genet. 2009 Jan;5(1):e1000350
references.pmid: 19165329
references.citation: Nat Genet. 2005 Apr;37(4):349-50
references.pmid: 15793589
references.citation: EMBO J. 1997 Oct 15;16(20):6209-16
references.pmid: 9321400