How strong is the evidence that Parkinson's disease is a prion disorder?

Current Opinion in Neurology

Volumn 29, Issue 4, 2016, Pages 459-466

  Brundin, Patrik ^a   Ma, Jiyan ^a   Kordower, Jeffrey H ^a,b  

^a VAN ANDEL RESEARCH INSTITUTE   (United States)

^b RUSH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Lewy body; Parkinson's disease; prion like; synuclein

Indexed keywords

ALPHA SYNUCLEIN; PRION PROTEIN; PRION;

DOPAMINERGIC NERVE CELL; HUMAN; INTESTINE INNERVATION; LEWY BODY; MOTONEURON NUCLEUS; NERVE FIBER TRANSPORT; NEUROPATHOLOGY; PARKINSON DISEASE; PATHOGENESIS; REVIEW; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PRION; PRION DISEASES; PROTEIN FOLDING;

ALPHA-SYNUCLEIN; HUMANS; PARKINSON DISEASE; PRION DISEASES; PRIONS; PROTEIN FOLDING;

EID: 84973345168     PISSN: 13507540     EISSN: 14736551     Source Type: Journal    
DOI: 10.1097/WCO.0000000000000349     Document Type: Review

References (106)

1. Halliday GM, Holton JL, Revesz T, Dickson DW. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 2011; 122:187-204.
2. Brundin P, Melki R, Kopito R. Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol 2010; 11:301-307.
3. Guo JL, Lee VM-Y. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 2014; 20:130-138.
4. Hardy J. Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: 'permissive templating' as a general mechanism underlying neurodegeneration. Biochem Soc Trans 2005; 33 (Pt 4):578-581.
5. Kordower JH, Chu Y, Hauser RA, et al. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 2008; 14:504-506.
6. Li J-Y, Englund E, Holton JL, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008; 14:501-503.
7. Kurowska Z, Englund E, Widner H, et al. Signs of degeneration in 12-22-year old grafts of mesencephalic dopamine neurons in patients with Parkinson's disease. J Parkinsons Dis 2011; 1:83-92.
8. Li J-Y, Englund E, Widner H, et al. Characterization of Lewy body pathology in 12-and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord 2010; 25:1091-1096.
9. Ahn T-B, Langston JW, Aachi VR, Dickson DW. Relationship of neighboring tissue and gliosis to a-synuclein pathology in a fetal transplant for Parkinson's disease. Am J Neurodegener Dis 2012; 1:49-59.
10. Cooper O, Astradsson A, Hallett P, et al. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients. J Neurol 2009; 256 (Suppl 3):310-316.
11. Chu Y, Kordower JH. Lewy body pathology in fetal grafts. Ann N Y Acad Sci 2010; 1184:55-67.
12. Brundin P, Kordower JH. Neuropathology in transplants in Parkinson's disease: Implications for disease pathogenesis and the future of cell therapy. In: Functional Neural Transplantation III. 1st ed Elsevier B. V.; 2012. p. 21.
13. Li W, Englund E, Widner H, et al. Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating Parkinsonian brain. Proc Natl Acad Sci USA 2016. [Epub ahead of print]
14. Brundin P, Li J-Y, Holton JL, et al. Research in motion: the enigma of Parkinson's disease pathology spread. Nat Rev Neurosci 2008; 9:741-745.
15. Braak H, Bohl JR, Müller CM, et al. Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Mov Disord 2006; 21:2042-2051.
16. Braak H, Ghebremedhin E, Rüb U, et al. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 2004; 318:121-134.
17. Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 2003; 110:517-536.
18. Hawkes CH, Del Tredici K, Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 2007; 33:599-614.
19. Hawkes CH, Del Tredici K, Braak H. Parkinson's disease: the dual hit theory revisited. Ann N Y Acad Sci 2009; 1170:615-622.
20. Cookson MR, van der Brug M. Cell systems and the toxic mechanism(s) of a-synuclein. Exp Neurol 2008; 209:5-11.
21. El-Agnaf OMA, Salem SA, Paleologou KE, et al. Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 2003; 17:1945-1947.
22. Lee S-J. Origins and effects of extracellular alpha-synuclein: implications in Parkinson's disease. J Mol Neurosci 2008; 34:17-22.
23. Lee H-J, Patel S, Lee S-J. Intravesicular localization and exocytosis of alphasynuclein and its aggregates. J Neurosci 2005; 25:6016-6024.
24. Hansen C, Angot E, Bergström A-L, et al. a-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 2011; 121:715-725.
25. Reyes JF, Olsson TT, Lamberts JT, et al. A cell culture model for monitoring a-synuclein cell-to-cell transfer. Neurobiol Dis 2015; 77:266-275.
26. Bae E-J, Lee H-J, Lee S-J. Cell models to study cell-to-cell transmission of a-synuclein. Methods Mol Biol 2016; 1345:291-298.
27. Luk KC, Song C, O'Brien P, et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci U S A 2009; 106:20051-20056.
28. Volpicelli-Daley LA, Luk KC, Patel TP, et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011; 72:57-71.
29. Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M. Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases. J Biol Chem 2010; 285:34885-34898.
30. Desplats P, Lee H-J, Bae E-J, et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A 2009; 106:13010-13015.
31. Angot E, Steiner JA, Lema ToméCM, et al. Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo. PLoS One 2012; 7:e39465.
32. Kordower JH, Dodiya HB, Kordower AM, et al. Transfer of host-derived alpha synuclein to grafted dopaminergic neurons in rat. Neurobiol Dis 2011; 43:1-
33. Luk KC, Kehm VM, Zhang B, et al. Intracerebral inoculation of pathological a-synuclein initiates a rapidly progressive neurodegenerative a-synucleinopathy in mice. J Exp Med 2012; 209:975-986.
34. Mougenot AL, Nicot S, Bencsik A, et al. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 2011; 33:1-4.
35. Recasens A, Dehay B, BovéJ, et al. Lewy body extracts from Parkinson disease brains trigger a-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 2014; 75:351-362.
36. Prusiner SB, Woerman AL, Mordes DA, et al. Evidence for a-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A 2015; 112:E5308-E5317.
37. Watts JC, Giles K, Oehler A, et al. Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci U S A 2013; 110:19555-19560.
38. Paumier KL, Luk KC, Manfredsson FP, et al. Intrastriatal injection of preformed mouse a-synuclein fibrils into rats triggers a-synuclein pathology and bilateral nigrostriatal degeneration. Neurobiol Dis 2015; 82:185-199.
39. Sacino AN, Brooks M, Thomas MA, et al. Intramuscular injection of a-synuclein induces CNS a-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A 2014; 111:10732-10737.
40. Peelaerts W, Bousset L, Van der Perren A, et al. a-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 2015; 522:340-344.
41. Rey NL, George S, Brundin P. Review: Spreading the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein. Neuropathol Appl Neurobiol 2016; 42:51-76.
42. Sacino AN, Brooks M, McKinney AB, et al. Brain injection of a-synuclein induces multiple proteinopathies, gliosis, and a neuronal injury marker. J Neurosci 2014; 34:12368-12378.
43. Masuda-Suzukake M, Nonaka T, Hosokawa M, et al. Prion-like spreading of pathological a-synuclein in brain. Brain 2013; 136 (Pt 4):1128-1138.
44. Bousset L, Pieri L, Ruiz-Arlandis G, et al. Structural and functional characterization of two alpha-synuclein strains. Nat Commun 2013; 4:2575.
45. Melki R. Role of different alpha-synuclein strains in synucleinopathies, similarities with other neurodegenerative diseases. J Parkinsons Dis 2015; 5:217-227.
46. Angot E, Steiner JA, Hansen C, et al. Are synucleinopathies prion-like disorders? Lancet Neurol 2010; 9:1128-1138.
47. Braak H, de Vos RAI, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 2006; 396:67-72.
48. Beach TG, White CL, Hladik CL, et al. Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders. Acta Neuropathol 2009; 117:169-174.
49. Postuma RB, Aarsland D, Barone P, et al. Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. Mov Disord 2012; 27:617-626.
50. Duda JE. Olfactory system pathology as a model of Lewy neurodegenerative disease. J Neurol Sci 2010; 289:49-54.
51. Lebouvier T, Chaumette T, Paillusson S, et al. The second brain and Parkinson's disease. Eur J Neurosci 2009; 30:735-741.
52. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease. Mov Disord 2015; 30:1600-1611.
53. Saper CB, Wainer BH, German DC. Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer's disease. Neuroscience 1987; 23:389-398.
54. Rey NL, Petit GH, Bousset L, et al. Transfer of human a-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol 2013; 126:555-573.
55. Svensson E, Horváth-PuhóE, Thomsen RW, et al. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol 2015; 78:522-529.
56. Derkinderen P, Shannon KM, Brundin P. Gut feelings about smoking and coffee in Parkinson's disease. Mov Disord 2014; 29:976-979.
57. Scheperjans F, Pekkonen E, Kaakkola S, Auvinen P. Linking smoking, coffee, urate, and Parkinson's disease: a role for gut microbiota? J Parkinsons Dis 2015; 5:255-262.
58. Devos D, Lebouvier T, Lardeux B, et al. Colonic inflammation in Parkinson's disease. Neurobiol Dis 2013; 50:42-48.
59. Forsyth CB, Shannon KM, Kordower JH, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One 2011; 6:e28032.
60. Holmqvist S, Chutna O, Bousset L, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 2014; 128:805-820.
61. Ulusoy A, Rusconi R, Pérez-Revuelta BI, et al. Caudo-rostral brain spreading of a-synuclein through vagal connections. EMBO Mol Med 2013; 5:1051-1059.
62. Ulusoy A, Musgrove RE, Rusconi R, et al. Neuron-to-neuron a-synuclein propagation in vivo is independent of neuronal injury. Acta Neuropathologica Communications 2015; 3:13.
63. Tyson T, Steiner JA, Brundin P. Sorting out release, uptake and processing of a-synuclein during prion-like spread of pathology. J Neurochem 2015. [Epub ahead of print]
64. Vekrellis K, Xilouri M, Emmanouilidou E, et al. Pathological roles of a-synuclein in neurological disorders. Lancet Neurol 2011; 10:1015-1025.
65. Emmanouilidou E, Minakaki G, Keramioti MV, et al. GABA transmission via ATP-dependent K channels regulates a-synuclein secretion in mouse striatum. Brain 2016; 139 (Pt 3):871-890.
66. Lee H-J, Cho E-D, Lee K-W, et al. Autophagic failure promotes the exocytosis and intercellular transfer of a-synuclein. Exp Mol Med 2013; 45:e22.
67. Lee H-J, Khoshaghideh F, Patel S, Lee S-J. Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway. J Neurosci 2004; 24:1888-1896.
68. Alvarez-Erviti L, Seow Y, Schapira AH, et al. Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 2011; 42:360-367.
69. Emmanouilidou E, Vekrellis K. Exocytosis and spreading of normal and aberrant a-synuclein. Brain Pathol 2016; 26:398-403.
70. Bae EJ, Yang NY, Lee C, et al. Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of a-synuclein aggregates. Cell Death Dis 2015; 6:e1901.
71. Danzer KM, Kranich LR, Ruf WP, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012; 7:42.
72. Emmanouilidou E, Melachroinou K, Roumeliotis T, et al. Cell-produced alphasynuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010; 30:6838-6851.
73. Grey M, Dunning CJ, Gaspar R, et al. Acceleration of a-synuclein aggregation by exosomes. J Biol Chem 2015; 290:2969-2982.
74. Lee H-J, Suk J-E, Bae E-J, et al. Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein. Int J Biochem Cell Biol 2008; 40:1835-1849.
75. Holmes BB, Devos SL, Kfoury N, et al. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci U S A 2013; 110:E3138-E3147.
76. Clayton EL, Evans GJO, Cousin MA. Bulk synaptic vesicle endocytosis is rapidly triggered during strong stimulation. J Neurosci 2008; 28:6627-6632.
77. Sung JY, Kim J, Paik SR, et al. Induction of neuronal cell death by Rab5Adependent endocytosis of alpha-synuclein. J Biol Chem 2001; 276:27441-27448.
78. Spencer B, Kim C, Gonzalez T, et al. a-Synuclein interferes with the ESCRTIII complex contributing to the pathogenesis of Lewy body disease. Hum Mol Genet 2016; 25:1100-1115.
79. Konno M, Hasegawa T, Baba T, et al. Suppression of dynamin GTPase decreases a-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. Mol Neurodegener 2012; 7:38.
80. Freeman D, Cedillos R, Choyke S, et al. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. PLoS One 2013; 8:e62143.
81. Brahic M, Bousset L, Bieri G, et al. Axonal transport and secretion of fibrillar forms of a-synuclein, Ab42 peptide and HTTExon 1. Acta Neuropathol 2016; 131:1-10.
82. Lamberts JT, Hildebrandt EN, Brundin P. Spreading of a-synuclein in the face of axonal transport deficits in Parkinson's disease: a speculative synthesis. Neurobiol Dis 2015; 77:276-283.
83. Reyes JF, Rey NL, Bousset L, et al. Alpha-synuclein transfers from neurons to oligodendrocytes. Glia 2014; 62:387-398.
84. Lee H-J, Suk J-E, Patrick C, et al. Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 2010; 285:9262-9272.
85. Lee H-J, Suk J-E, Bae E-J, Lee S-J. Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. Biochem Biophys Res Commun 2008; 372:423-428.
86. Park J-Y, Kim KS, Lee S-B, et al. On the mechanism of internalization of a-synuclein into microglia: roles of ganglioside GM1 and lipid-raft. J Neurochem 2009; 110:400-411.
87. Fellner L, Jellinger KA, Wenning GK, Stefanova N. Glial dysfunction in the pathogenesis of a-synucleinopathies: emerging concepts. Acta Neuropathol 2011; 121:675-693.
88. Bae E-J, Lee H-J, Rockenstein E, et al. Antibody-aided clearance of extracellular a-synuclein prevents cell-to-cell aggregate transmission. J Neurosci 2012; 32:13454-13469.
89. Tran HT, Chung CH-Y, Iba M, et al. a-Synuclein immunotherapy blocks uptake and templated propagation of misfolded a-synuclein and neurodegeneration. Cell Rep 2014; 7:2054-2065.
90. George S, Brundin P. Immunotherapy in Parkinson's disease: micromanaging alpha-synuclein aggregation. J Parkinsons Dis 2015; 5: 413-424.
91. Lee JS, Lee S-J. Mechanism of antia-synuclein immunotherapy. J Mov Disord 2016; 9:14-19.
92. Lindström V, Ihse E, Fagerqvist T, et al. Immunotherapy targeting a-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders. Immunotherapy 2014; 6:141-153.
93. Games D, Valera E, Spencer B, et al. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models. J Neurosci 2014; 34:9441-9454.
94. Asi YT, Simpson JE, Heath PR, et al. Alpha-synuclein mRNA expression in oligodendrocytes in MSA. Glia 2014; 62:964-970.
95. Djelloul M, Holmqvist S, Boza-Serrano A, et al. Alpha-synuclein expression in the oligodendrocyte lineage: an in vitro and in vivo study using rodent and human models. Stem Cell Rep 2015; 5:174-184.
96. Decressac M, Mattsson B, Weikop P, et al. TFEB-mediated autophagy rescues midbrain dopamine neurons from a-synuclein toxicity. Proc Natl Acad Sci U S A 2013; 110:E1817-E1826.
97. Pérez-Revuelta BI, Hettich MM, Ciociaro A, et al. Metformin lowers Ser-129 phosphorylated a-synuclein levels via mTOR-dependent protein phosphatase 2A activation. Cell Death Dis 2014; 5:e1209.
98. Wagner J, Ryazanov S, Leonov A, et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol 2013; 125:795-813.
99. Levin J, Schmidt F, Boehm C, et al. The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset. Acta Neuropathol 2014; 127:779-780.
100. Adler CH, Dugger BN, Hinni ML, et al. Submandibular gland needle biopsy for the diagnosis of Parkinson disease. Neurology 2014; 82:858-864.
101. Beach TG, Adler CH, Serrano G, et al. Prevalence of submandibular gland synucleinopathy in Parkinson's disease, dementia with Lewy bodies and other Lewy body disorders. J Parkinsons Dis 2016; 6:153-163.
102. CorbilléA-G, Clairembault T, Coron E, et al. What a gastrointestinal biopsy can tell us about Parkinson's disease? Neurogastroenterol Motil 2016. [Epub ahead of print]
103. Shannon KM, Keshavarzian A, Dodiya HB, et al. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord 2012; 27:716-719.
104. Visanji NP, Marras C, Kern DS, et al. Colonic mucosal a-synuclein lacks specificity as a biomarker forParkinson disease. Neurology 2015;84:609-616.
105. Irwin DJ, Abrams JY, Schonberger LB, et al. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 2013; 70:462-468.
106. Brown P, Brandel J-P, Sato T, et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis 2012; 18:901-907.