Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice

Movement Disorders

Volumn 29, Issue 12, 2014, Pages 1476-1485

  Cooper, J Mark ^a   Wiklander, P B Oscar ^b   Nordin, Joel Z ^b   Al Shawi, Raya ^c   Wood, Matthew J ^d   Vithlani, Mansi ^a   Schapira, Anthony H V ^a   Simons, J Paul ^c   El Andaloussi, Samir ^b,d   Alvarez Erviti, Lydia ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b KAROLINSKA INSTITUTE   (Sweden)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

RVG exosomes; siRNA; Transgenic mice; Syn

Indexed keywords

ALPHA SYNUCLEIN; MESSENGER RNA; PROTEIN AGGREGATE; RAVIES PROTEIN; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VIRUS GLYCOPROTEIN; GLYCOPROTEIN; PEPTIDE FRAGMENT; RABIES VIRUS GLYCOPROTEIN PEPTIDE; VIRUS PROTEIN;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ARTICLE; BRAIN LEVEL; CONTROLLED STUDY; DENDRITIC CELL; DOPAMINERGIC NERVE CELL; DOWN REGULATION; EXOSOME; GENE DELIVERY SYSTEM; IN VITRO STUDY; MOUSE; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SUBSTANTIA NIGRA; TRANSGENIC MOUSE; ANIMAL; BRAIN; C57BL MOUSE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENE VECTOR; GENETIC TRANSFECTION; GENETICS; HUMAN; METABOLISM; MUTATION; NEUROBLASTOMA; PATHOLOGY; PHYSIOLOGY; TIME; TUMOR CELL LINE;

ALPHA-SYNUCLEIN; ANIMALS; BRAIN; CELL LINE, TUMOR; DENDRITIC CELLS; EXOSOMES; GENE EXPRESSION REGULATION; GENETIC VECTORS; GLYCOPROTEINS; HUMANS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUTATION; NEUROBLASTOMA; PEPTIDE FRAGMENTS; RNA, MESSENGER; RNA, SMALL INTERFERING; TIME FACTORS; TRANSFECTION; VIRAL PROTEINS;

EID: 84924536514     PISSN: 08853185     EISSN: 15318257     Source Type: Journal    
DOI: 10.1002/mds.25978     Document Type: Article

References (25)

1. Lee VM, Trojanowski JQ. Mechanisms of Parkinson's disease linked to pathological α-Syn: new targets for drug discovery. Neuron 2006;52:33-38.
2. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24:197-211.
3. Jellinger K. A critical evaluation of current staging of α-Syn pathology in Lewy body disorders. Biochim Biophys Acta 2009;1792:730-740.
4. Lewis J, Melrose H, Bumcrot D, Hope A, Zehr C, Lincoln S, et al. In vivo silencing of α-Syn using naked siRNA. Mol Neurodegener 2008;3:19.
5. Maysinger D, Morinville A. Drug delivery to the nervous system. Trends Biotechnol 1997;15:410-418.
6. Coune PG, Schneider BL, Aebischer P. Parkinson's disease: gene therapies. Cold Spring Harb Perspect Med 2012;2:a009431.
7. Zhang Y, Pardridge WM. Near complete rescue of experimental Parkinson's disease with intravenous, non-viral GDNF gene therapy. Pharm Res. 2009;26:1059-1063.
8. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011;29:341-345.
9. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-659.
10. Alvarez-Erviti L, Seow Y, Schapira AH, Rodriguez-Oroz MC, Obeso JA, Cooper JM. Influence of microRNA deregulation on chaperone-mediated autophagy and α-synuclein pathology in Parkinson's disease. Cell Death Dis 2013;4:e545.
11. Azeredo da Silveira S, Schneider BL, Cifuentes-Diaz C, et al. Phosphorylation does not prompt, nor prevent, the formation of α-Syn toxic species in a rat model of Parkinson's disease. Hum Mol Genet 2009;18:872-887.
12. Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ et al. Phosphorylation of Ser-129 is the dominant pathological modification of α-Syn in familial and sporadic Lewy body disease. J Biol Chem 2006;281:29739-29752.
13. Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E, Levine MS, Chesselet MF. Early and progressive sensorimotor anomalies in mice overexpressing wild-type human α-Syn. J Neurosci 2004;24:9434-9440.
14. Singleton AB, Farrer M, Johnson J, et al. Alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003;302:841.
15. Chartier-Harlin MC, Kachergus J, Roumier C, et al. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004;364:1167-1169.
16. Danzer KM, Haasen D, Karow AR, et al. Different species of α-Syn oligomers induce calcium influx and seeding. J Neurosci 2007;27:9220-9232.
17. Abeliovich A, Schmitz Y, Fariñas I, et al. Mice lacking α-Syn display functional deficits in the nigrostriatal dopamine system. Neuron 2000;25:239-252.
18. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012;338:949-953.
19. Recasens A, Dehay B, Bové J, et al. Lewy body extracts from parkinson's disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 2014; DOI: 10.1002/ana.24066.
20. Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson's disease. Neuron 2010;66:646-661.
21. Fujiwara H, Hasegawa M, Dohmae N, et al. Alpha-synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 2002;4:160-164.
22. Fujiwara H, Hasegawa M, Dohmae N, et al. Alpha-synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol 2002;4:160-164.
23. Febbraro F, Sahin G, Farran A, et al. Ser129D mutant α-Syn induces earlier motor dysfunction while S129A results in distinctive pathology in a rat model of Parkinson's disease. Neurobiol Dis 2013;56, 47-58.
24. Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000;101:57-66.
25. DiFiglia, M, Sena-Esteves M, Chase K, et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci U S A 2007;104:17204-17209.