Intramuscular injection of α-synuclein induces CNS α-synuclein pathology and a rapid-onset motor phenotype in transgenic mice

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 29, 2014, Pages 10732-10737

  Sacino, Amanda N ^a   Brooks, Mieu ^a   Thomas, Michael A ^a   McKinney, Alex B ^a   Lee, Sooyeon ^a   Regenhardt, Robert W ^a   McGarvey, Nicholas H ^a   Ayers, Jacob I ^a   Notterpek, Lucia ^a   Borchelt, David R ^a   Golde, Todd E ^a   Giasson, Benoit I ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Amyloid; Parkinson disease

Indexed keywords

ALANINE; ALPHA SYNUCLEIN; THREONINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTOSIS; CENTRAL NERVOUS SYSTEM; COMPLETE SCIATIC NERVE TRANSECTION INJURY; CONTROLLED STUDY; GLIOSIS; MOTOR DYSFUNCTION; MOUSE; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; PARKINSON DISEASE; PHENOTYPE; PRION DISEASE; PRIORITY JOURNAL; SPINAL CORD; TRANSGENIC MOUSE;

AMYLOID; PARKINSON DISEASE;

ALPHA-SYNUCLEIN; ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; INJECTIONS, INTRAMUSCULAR; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOTOR ACTIVITY; PHENOTYPE; SURVIVAL ANALYSIS;

EID: 84904636970     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1321785111     Document Type: Article

References (57)

1. Cookson MR (2005) The biochemistry of Parkinson's disease. Annu Rev Biochem 74: 29-52.
2. Gasser T (2009) Mendelian forms of Parkinson's disease. Biochim Biophys Acta 1792(7): 587-596.
3. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2(7):492-501.
4. Waxman EA, Giasson BI (2009) Molecular mechanisms of alpha-synuclein neurodegeneration. Biochim Biophys Acta 1792(7):616-624.
5. Polymeropoulos MH, et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276(5321):2045-2047. (Pubitemid 27443610)
6. Krüger R, et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18(2):106-108.
7. Zarranz JJ, et al. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55(2):164-173. (Pubitemid 38166992)
8. Farrer M, et al. (2004) Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol 55(2):174-179. (Pubitemid 38166993)
9. Singleton AB, et al. (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302(5646):841. (Pubitemid 37339619)
10. Kiely AP, et al. (2013) α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson's disease and multiple system atrophy? Acta Neuropathol 125(5): 753-769.
11. Proukakis C, et al. (2013) A novel α-synuclein missense mutation in Parkinson disease. Neurology 80(11):1062-1064.
12. Dawson T, Mandir A, Lee M (2002) Animal models of PD: Pieces of the same puzzle? Neuron 35(2):219-222. (Pubitemid 34876725)
13. Braak H, Rüb U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110(5):517-536.
14. Braak H, et al. (2006) Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Mov Disord 21(12):2042-2051. (Pubitemid 46140410)
15. Braak H, et al. (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24(2):197-211. (Pubitemid 36007810)
16. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14(5):504-506. (Pubitemid 351655212)
17. Li JY, et al. (2008) Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14(5):501-503.
18. Li JY, et al. (2010) Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord 25(8):1091-1096.
19. Wakabayashi K, Mori F, Tanji K, Orimo S, Takahashi H (2010) Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol 120(1):1-12.
20. Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 396(1):67-72. (Pubitemid 43233790)
21. Luk KC, et al. (2012) Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice. J Exp Med 209(5): 975-986.
22. Luk KC, et al. (2012) Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109):949-953.
23. Watts JC, et al. (2013) Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci USA 110(48):19555-19560.
24. Mougenot AL, et al. (2012) Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 33(9):2225-2228.
25. Masuda-Suzukake M, et al. (2013) Prion-like spreading of pathological α-synuclein in brain. Brain 136(Pt 4):1128-1138.
26. Recasens A, et al. (2014) Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 75(3):351-362.
27. Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501(7465):45-51.
28. Polymenidou M, Cleveland DW (2012) Prion-like spread of protein aggregates in neurodegeneration. J Exp Med 209(5):889-893.
29. Uryu K, et al. (2003) Age-dependent synuclein pathology following traumatic brain injury in mice. Exp Neurol 184(1):214-224. (Pubitemid 37444032)
30. Giasson BI, et al. (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521-533. (Pubitemid 34628750)
31. Emmer KL, Waxman EA, Covy JP, Giasson BI (2011) E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with agedependent, detrimental motor impairment. J Biol Chem 286(40):35104-35118.
32. Luk KC, et al. (2009) Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 106(47): 20051-20056.
33. Sacino AN, et al. (2013) Conformational templating of α-synuclein aggregates in neuronal-glial cultures. Mol Neurodegener 8:17.
34. Waxman EA, Giasson BI (2010) A novel, high-efficiency cellular model of fibrillar alpha-synuclein inclusions and the examination of mutations that inhibit amyloid formation. J Neurochem 113(2):374-388.
35. Waxman EA, Giasson BI (2011) Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau. J Neurosci 31(21):7604-7618.
36. Giasson BI, Murray IV, Trojanowski JQ, Lee VMY (2001) A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem 276(4):2380-2386.
37. Waxman EA, Mazzulli JR, Giasson BI (2009) Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization. Biochemistry 48(40):9427-9436.
38. Kim C, et al. (2013) Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun 4:1562.
39. Fellner L, et al. (2013) Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia 61(3):349-360.
40. Codolo G, et al. (2013) Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS ONE 8(1):e55375.
41. Kuusisto E, Parkkinen L, Alafuzoff I (2003) Morphogenesis of Lewy bodies: Dissimilar incorporation of alpha-synuclein, ubiquitin, and p62. J Neuropathol Exp Neurol 62(12):1241-1253. (Pubitemid 37494193)
42. Giasson BI, Duda JE, Forman MS, Lee VMY, Trojanowski JQ (2001) Prominent perikaryal expression of α- and β-synuclein in neurons of dorsal root ganglion and in medullary neurons. Exp Neurol 172(2):354-362. (Pubitemid 34075084)
43. Kimberlin RH, Cole S, Walker CA (1987) Pathogenesis of scrapie is faster when infection is intraspinal instead of intracerebral. Microb Pathog 2(6):405-415. (Pubitemid 17109082)
44. Giasson BI, Uryu K, Trojanowski JQ, Lee VMY (1999) Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 274(12):7619-7622.
45. Conway KA, Harper JD, Lansbury PT (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 4(11): 1318-1320. (Pubitemid 28512115)
46. Narhi L, et al. (1999) Both familial Parkinson's disease mutations accelerate alphasynuclein aggregation. J Biol Chem 274(14):9843-9846.
47. Rey NL, Petit GH, Bousset L, Melki R, Brundin P (2013) Transfer of human α-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol 126(4):555-573.
48. Clavaguera F, et al. (2014) Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice. Acta Neuropathol 127(2):299-301.
49. Eisele YS, et al. (2010) Peripherally applied Abeta-containing inoculates induce cerebral β-amyloidosis. Science 330(6006):980-982.
50. Eisele YS, et al. (2009) Induction of cerebral β-amyloidosis: Intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci USA 106(31):12926-12931.
51. Sacino AN, et al. (2013) Induction of CNS α-synuclein pathology by fibrillar and nonamyloidogenic recombinant α-synuclein. Acta Neuropathol Commun 1(1):38.
52. Sacino AN, et al. (2014) Amyloidogenic α-synuclein seeds do not invariably induce rapid, widespread pathology in mice. Acta Neuropathol 127(5):645-665.
53. Golde TE, Borchelt DR, Giasson BI, Lewis J (2013) Thinking laterally about neurodegenerative proteinopathies. J Clin Invest 123(5):1847-1855.
54. Rivers RC, et al. (2008) Molecular determinants of the aggregation behavior of alphaand beta-synuclein. Protein Sci 17(5):887-898. (Pubitemid 351629583)
55. Telling GC, et al. (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83(1): 79-90.
56. Abeliovich A, et al. (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25(1):239-252. (Pubitemid 30316525)
57. Waxman EA, Duda JE, Giasson BI (2008) Characterization of antibodies that selectively detect alpha-synuclein in pathological inclusions. Acta Neuropathol 116(1):37-46.