title: Autophagy and neurodegeneration.
abstract: Most neurodegenerative diseases that afflict humans are associated with the intracytoplasmic deposition of aggregate-prone proteins in neurons. Autophagy is a powerful process for removing such proteins. In this Review, we consider how certain neurodegenerative diseases may be associated with impaired autophagy and how this may affect pathology. We also discuss how autophagy induction may be a plausible therapeutic strategy for some conditions and review studies in various models that support this hypothesis. Finally, we briefly describe some of the signaling pathways that may be amenable to therapeutic targeting for these goals.
authors: Rebecca A
authors: RA
authors: Frake
authors: Thomas
authors: T
authors: Ricketts
authors: Fiona M
authors: FM
authors: Menzies
authors: David C
authors: DC
authors: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
references: J Neuropathol Exp Neurol. 2008 Apr;67(4):366-74
references: 18379432
references: Nat Chem Biol. 2008 May;4(5):295-305
references: 18391949
references: J Neurochem. 2008 May;105(3):1048-56
references: 18182054
references: Autophagy. 2008 May;4(4):457-66
references: 18253089
references: J Cell Sci. 2008 May 15;121(Pt 10):1649-60
references: 18430781
references: J Clin Invest. 2008 Jun;118(6):2190-9
references: 18497889
references: J Neurosci. 2008 Jul 2;28(27):6926-37
references: 18596167
references: Mol Biol Cell. 2009 Apr;20(7):1992-2003
references: 19225151
references: Neurobiol Aging. 2012 Oct;33(10):2291-305
references: 22169203
references: Autophagy. 2012 Apr;8(4):609-22
references: 22361619
references: Nat Rev Drug Discov. 2012 Sep;11(9):709-30
references: 22935804
references: J Neurosci. 2012 Sep 5;32(36):12396-405
references: 22956830
references: Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15024-9
references: 22932872
references: IUBMB Life. 2012 Oct;64(10):801-8
references: 22815132
references: Am J Hum Genet. 2012 Dec 7;91(6):1144-9
references: 23176820
references: Cancer Res. 2007 Jul 15;67(14):6745-52
references: 17638885
references: Curr Neurol Neurosci Rep. 2007 Sep;7(5):428-33
references: 17764634
references: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14489-94
references: 17726112
references: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19023-8
references: 18024584
references: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19262-6
references: 18040046
references: Hum Mol Genet. 2008 Jan 15;17(2):170-8
references: 17921520
references: J Alzheimers Dis. 2007 Dec;12(4):365-75
references: 18198423
references: Nat Genet. 2013 Jan;45(1):83-7
references: 23222957
references: J Cell Biol. 2013 Mar 18;200(6):731-41
references: 23479740
references: Mol Cell Neurosci. 2013 Jul;55:37-43
references: 22926193
references: Nat Genet. 2013 Apr;45(4):445-9, 449e1
references: 23435086
references: Acta Neuropathol. 2013 Apr;125(4):511-22
references: 23417734
references: J Cell Sci. 2013 Jan 15;126(Pt 2):580-92
references: 23178947
references: Curr Alzheimer Res. 2013 May 1;10(4):433-41
references: 23305067
references: Aging Cell. 2013 Jun;12(3):370-80
references: 23425014
references: Cell Struct Funct. 2008;33(1):109-22
references: 18388399
references: J Cell Biol. 2008 Oct 6;183(1):101-16
references: 18838554
references: J Cell Biol. 2008 Dec 1;183(5):795-803
references: 19029340
references: Nat Genet. 2009 Feb;41(2):163-5
references: 19136952
references: J Biol Chem. 2009 Mar 20;284(12):8023-32
references: 19150980
references: Mol Biol Cell. 2009 Apr;20(7):1981-91
references: 19211835
references: Cell Mol Life Sci. 2013 Jan;70(1):121-36
references: 22773119
references: Mol Neurodegener. 2012;7:48
references: 22998728
references: Autophagy. 2012 Nov;8(11):1686-7
references: 22874558
references: Neurology. 2013 Jan 29;80(5):458-63
references: 23303844
references: Mov Disord. 2013 Jan;28(1):14-23
references: 23389780
references: Nature. 2013 Feb 14;494(7436):201-6
references: 23364696
references: Am J Hum Genet. 2001 Apr;68(4):895-900
references: 11254447
references: Hum Mol Genet. 2002 May 1;11(9):1107-17
references: 11978769
references: Am J Hum Genet. 2002 Jun;70(6):1582-8
references: 11992264
references: Nat Genet. 2003 Apr;33(4):455-6
references: 12627231
references: J Biol Chem. 2003 Jul 4;278(27):25009-13
references: 12719433
references: Science. 2003 Oct 31;302(5646):841
references: 14593171
references: Science. 2004 May 21;304(5674):1158-60
references: 15087508
references: Nat Genet. 2004 Jun;36(6):585-95
references: 15146184
references: Neuroreport. 2004 Jun 7;15(8):1325-8
references: 15167559
references: J Neuropathol Exp Neurol. 2004 Aug;63(8):821-30
references: 15330337
references: Nature. 1991 Feb 21;349(6311):704-6
references: 1671712
references: Cell. 1993 Mar 26;72(6):971-83
references: 8458085
references: J Biol Chem. 1995 Feb 3;270(5):2320-6
references: 7836465
references: Nature. 1995 Jun 29;375(6534):754-60
references: 7596406
references: Science. 1995 Aug 18;269(5226):973-7
references: 7638622
references: J Biol Chem. 1995 Nov 17;270(46):27531-7
references: 7499212
references: EMBO J. 1995 Dec 1;14(23):5892-907
references: 8846782
references: J Biol Chem. 1998 Feb 13;273(7):3963-6
references: 9461583
references: Nature. 1998 Apr 9;392(6676):605-8
references: 9560156
references: Mol Cell Biol. 2005 Feb;25(3):1025-40
references: 15657430
references: J Neuropathol Exp Neurol. 2005 Feb;64(2):113-22
references: 15751225
references: Nat Genet. 2005 Jul;37(7):771-6
references: 15980862
references: J Cell Biol. 2005 Sep 26;170(7):1101-11
references: 16186256
references: J Cell Biol. 2005 Oct 10;171(1):87-98
references: 16203860
references: Ann Neurol. 2005 Dec;58(6):909-19
references: 16315276
references: Hum Mol Genet. 2006 Feb 1;15(3):433-42
references: 16368705
references: Hum Mol Genet. 2006 Feb 1;15(3):453-65
references: 16371423
references: Hum Mol Genet. 2006 Apr 1;15(7):1209-16
references: 16497721
references: J Biol Chem. 2006 May 19;281(20):14474-85
references: 16522639
references: Nature. 2006 Jun 15;441(7095):885-9
references: 16625204
references: Nature. 2006 Jun 15;441(7095):880-4
references: 16625205
references: Nat Genet. 2006 Oct;38(10):1184-91
references: 16964263
references: Nature. 2006 Oct 19;443(7113):780-6
references: 17051204
references: J Biol Chem. 2006 Nov 17;281(46):34870-9
references: 16990266
references: J Biol Chem. 2007 Feb 23;282(8):5641-52
references: 17182613
references: Cancer Res. 2007 Jun 15;67(12):5840-50
references: 17575152
references: Brain. 2013 Oct;136(Pt 10):3119-39
references: 24030950
references: Cell Rep. 2013 Oct 17;5(1):61-9
references: 24095740
references: Autophagy. 2013 Sep;9(9):1308-20
references: 23851366
references: Hum Mol Genet. 2013 Nov 15;22(22):4528-44
references: 23804751
references: Biochim Biophys Acta. 2013 Dec;1833(12):2900-10
references: 23916833
references: J R Soc Med. 2014 Jan;107(1):14-21
references: 24399773
references: J Biol Chem. 2014 Feb 7;289(6):3547-54
references: 24324270
references: Traffic. 2008 Apr;9(4):574-87
references: 18182013
references: PLoS One. 2013;8(6):e65367
references: 23750258
references: J Biol Chem. 2013 Jun 21;288(25):18249-59
references: 23677989
references: Hum Mol Genet. 2013 Aug 15;22(16):3315-28
references: 23666528
references: Mol Psychiatry. 2013 Aug;18(8):889-97
references: 22850627
references: J Neurosci. 2013 Aug 7;33(32):13138-49
references: 23926267
references: Neuron. 2013 Sep 4;79(5):873-86
references: 24012002
references: Neuroscience. 2014 Mar 28;263:111-24
references: 24418614
references: J Mol Med (Berl). 2014 Apr;92(4):373-86
references: 24337465
references: Pharmacol Res. 2014 Mar;81:54-63
references: 24602800
references: Autophagy. 2014 Apr;10(4):588-602
references: 24441414
references: Neurotherapeutics. 2014 Apr;11(2):433-49
references: 24477711
references: Nat Commun. 2014;5:3828
references: 24819384
references: Hum Mol Genet. 2014 Jul 1;23(13):3579-95
references: 24549040
references: Nat Chem Biol. 2014 Aug;10(8):677-85
references: 24974230
references: Neuroscience. 2013 Mar 1;232:90-105
references: 23262240
references: J Biol Chem. 2009 May 1;284(18):12297-305
references: 19258318
references: J Biol Chem. 2009 Aug 21;284(34):22657-63
references: 19542233
references: J Cell Biol. 2009 Sep 7;186(5):703-11
references: 19720874
references: Hum Mol Genet. 2009 Nov 1;18(21):4022-34
references: 19640926
references: J Neurosci. 2009 Oct 28;29(43):13578-88
references: 19864570
references: Brain. 2010 Jan;133(Pt 1):93-104
references: 20007218
references: Neuropathology. 2010 Feb 1;30(1):1-6
references: 19496938
references: PLoS Genet. 2010 Feb;6(2):e1000838
references: 20140187
references: PLoS One. 2010;5(2):e9313
references: 20174468
references: J Biol Chem. 2010 Mar 19;285(12):9100-13
references: 20080969
references: PLoS One. 2010;5(4):e9979
references: 20376313
references: J Biol Chem. 2010 Apr 23;285(17):13107-20
references: 20178983
references: J Cell Biol. 2010 Apr 19;189(2):211-21
references: 20404107
references: Nat Neurosci. 2010 May;13(5):567-76
references: 20383138
references: Hum Mol Genet. 2010 Jun 1;19(11):2144-53
references: 20190273
references: Nature. 2010 May 13;465(7295):223-6
references: 20428114
references: Hum Mol Genet. 2010 Jul 15;19(14):2867-76
references: 20453062
references: Nature. 2010 Jul 1;466(7302):68-76
references: 20562859
references: Cell. 2010 Jun 25;141(7):1146-58
references: 20541250
references: Cell. 2010 Jul 23;142(2):270-83
references: 20655468
references: Neurobiol Dis. 2010 Sep;39(3):423-38
references: 20546895
references: Hum Mol Genet. 2010 Sep 1;19(17):3413-29
references: 20566712
references: Hum Mol Genet. 2010 Oct 1;19(19):3702-20
references: 20616151
references: Hum Genet. 2010 Oct;128(4):453-9
references: 20697744
references: J Cell Biol. 2010 Sep 20;190(6):1023-37
references: 20855506
references: Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35
references: 21157483
references: Brain. 2011 Jan;134(Pt 1):258-77
references: 21186265
references: FASEB J. 2011 Jan;25(1):219-31
references: 20852062
references: Neurobiol Dis. 2011 Jul;43(1):68-78
references: 21081164
references: FASEB J. 2011 Jun;25(6):1934-42
references: 21368103
references: Mol Cell Biol. 2011 Jul;31(14):2867-76
references: 21576371
references: Science. 2011 Jul 8;333(6039):228-33
references: 21617041
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12937-42
references: 21768369
references: Dev Cell. 2011 Aug 16;21(2):343-57
references: 21802374
references: PLoS One. 2011;6(9):e25416
references: 21980451
references: Mol Cell. 2011 Oct 21;44(2):279-89
references: 22017874
references: Nat Rev Drug Discov. 2011 Nov;10(11):868-80
references: 22037041
references: Neurosci Lett. 2012 Jan 6;506(1):149-54
references: 22085693
references: Curr Biol. 2012 Jan 10;22(1):R29-34
references: 22240478
references: Hum Mol Genet. 2012 Feb 1;21(3):511-25
references: 22012985
references: Hum Mol Genet. 2012 Apr 1;21(7):1521-33
references: 22186026
references: Neurobiol Dis. 2012 Apr;46(1):101-8
references: 22249108
references: Acta Neuropathol. 2012 May;123(5):747-9
references: 22318854
references: PLoS One. 2012;7(4):e34713
references: 22514658
references: J Cell Sci. 2012 Mar 15;125(Pt 6):1488-99
references: 22275429
references: Mol Biol Cell. 2012 May;23(10):1860-73
references: 22456507
references: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9611-6
references: 22647602
references: Brain. 2012 Jul;135(Pt 7):2169-77
references: 22689910
references: Am J Hum Genet. 2012 Dec 7;91(6):1065-72
references: 23176824