title: Is Parkinson's disease truly a prion-like disorder? An appraisal of current evidence.
abstract: Parkinson's disease (PD) is the world's second most common neurodegenerative disease and most common movement disorder. Characterised by a loss of dopaminergic neurons and the development of intraneuronal inclusions known as Lewy bodies, it has classically been thought of as a cell-autonomous disease. However, in 2008, two groups reported the startling observation of Lewy bodies within embryonic neuronal grafts transplanted into PD patients little more than a decade previously, suggesting that PD pathology can be propagated to neighbouring cells and calling basic assumptions of our understanding of the disease into question. Subsequent research has largely served to confirm this interpretation, pointing towards a prion-like intercellular transfer of misfolded α-synuclein, the main component of Lewy bodies, as central to PD. This shift in thinking offers a revolutionary approach to PD treatment, potentially enabling a transition from purely symptomatic therapy to direct targeting of the pathology that drives disease progression. In this short review, we appraise current experimental support for PD as a prion-like disease, whilst highlighting areas of controversy or inconsistency which must be resolved. We also offer a brief discussion of the therapeutic implications of these discoveries.
authors: Hertford College, University of Oxford, Catte Street, Oxford OX1 3BW, UK.
authors: Aneesha
authors: 0000-0002-8598-6870
authors: A
authors: Chauhan
authors: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors: Alexander F
authors: 0000-0002-4004-3676
authors: AF
authors: Jeans
references: Annu Rev Neurosci. 2001;24:519-50
references: 11283320
references: Protein Sci. 2014 Oct;23(10):1369-79
references: 25044276
references: Mov Disord. 2011 May;26(6):1042-8
references: 21626549
references: Int J Biochem Cell Biol. 2008;40(9):1835-49
references: 18291704
references: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20051-6
references: 19892735
references: Lancet Neurol. 2009 Dec;8(12):1128-39
references: 19909911
references: Nature. 2011 Aug 14;477(7362):107-10
references: 21841800
references: PLoS One. 2010 Jan 19;5(1):e8762
references: 20098733
references: Expert Opin Ther Targets. 2012 Apr;16(4):421-32
references: 22480256
references: Sci Rep. 2012;2:898
references: 23205266
references: Nat Med. 2008 May;14(5):501-3
references: 18391963
references: Neurosci Lett. 2000 Jun 16;287(1):65-7
references: 10841992
references: J Biol Chem. 2002 Dec 13;277(50):49071-6
references: 12377775
references: Ann Neurol. 2003 Sep;54(3):403-14
references: 12953276
references: Am J Pathol. 2003 Jul;163(1):91-100
references: 12819014
references: PLoS One. 2014 Feb 21;9(2):e87388
references: 24586273
references: J Toxicol Environ Health A. 2011;74(22-24):1433-59
references: 22043906
references: PLoS One. 2012;7(6):e39465
references: 22737239
references: Neuropathol Appl Neurobiol. 2014 Feb;40(1):60-70
references: 24372386
references: J Neurosci. 2005 Jun 22;25(25):6016-24
references: 15976091
references: Prion. 2013 Jan-Feb;7(1):92-7
references: 23360753
references: Neurobiol Dis. 2011 Sep;43(3):552-7
references: 21600984
references: Mov Disord. 2008 Jun 15;23(8):1076-84
references: 18442121
references: Science. 2003 Oct 31;302(5646):841
references: 14593171
references: Nat Med. 2008 May;14(5):504-6
references: 18391962
references: Mov Disord. 2008 Dec 15;23(16):2303-6
references: 19006193
references: J Clin Invest. 2011 Feb;121(2):715-25
references: 21245577
references: BMC Neurosci. 2014 Jun 04;15:69
references: 24898419
references: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13010-5
references: 19651612
references: Physiol Rev. 2009 Oct;89(4):1105-52
references: 19789378
references: PLoS Pathog. 2007 Aug 31;3(8):e125
references: 17784787
references: Brain. 2013 Aug;136(Pt 8):2419-31
references: 23884810
references: Ann Neurol. 2003;53 Suppl 3:S3-12; discussion S12-5
references: 12666094
references: Nat Rev Neurosci. 2001 May;2(5):365-9
references: 11331920
references: Mol Neurodegener. 2012 Aug 24;7:42
references: 22920859
references: PLoS One. 2008 Apr 02;3(4):e1867
references: 18382657
references: Ann Neurol. 2013 Feb;73(2):155-69
references: 23225525
references: Acta Neuropathol Commun. 2013 May 08;1:2
references: 24252164
references: Nature. 1997 Aug 28;388(6645):839-40
references: 9278044
references: J Parkinsons Dis. 2011;1(3):277-86
references: 23939308
references: J Neurosci. 2011 Oct 12;31(41):14508-20
references: 21994367
references: Am J Manag Care. 2012 Sep;18(7 Suppl):S168-75
references: 23039865
references: Nat Cell Biol. 2002 Feb;4(2):160-4
references: 11813001
references: Brain Res. 1997 Nov 14;775(1-2):24-9
references: 9439824
references: Curr Alzheimer Res. 2010 Jun;7(4):307-22
references: 19860724
references: J Neurosci Res. 2007 Feb 1;85(2):351-63
references: 17131421
references: Science. 2012 Nov 16;338(6109):949-53
references: 23161999
references: Nat Cell Biol. 2009 Mar;11(3):328-36
references: 19198598
references: Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12956-60
references: 9789022
references: Science. 1982 Apr 9;216(4542):136-44
references: 6801762
references: Nat Med. 2008 May;14 (5):507-9
references: 18391961
references: Science. 1991 Jun 14;252(5012):1515-22
references: 1675487
references: N Engl J Med. 2001 Mar 8;344(10):710-9
references: 11236774
references: Neuron. 2011 Oct 6;72(1):57-71
references: 21982369
references: Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
references: 12498954
references: Lancet Neurol. 2006 Jun;5(6):525-35
references: 16713924
references: Nat Rev Neurosci. 2002 Dec;3(12):932-42
references: 12461550
references: Acta Neuropathol Commun. 2014 Aug 06;2:88
references: 25095794
references: JAMA Neurol. 2013 Apr;70(4):462-8
references: 23380910