In vivo demonstration that alpha-synuclein oligomers are toxic.
作者： B. Winner , R. Jappelli , S. K. Maji , P. A. Desplats , L. Boyer
关键词: Mutant 、 Substantia nigra 、 Fibril 、 Dopaminergic 、 Oligomer 、 Biology 、 Monomer 、 Biochemistry 、 In vivo 、 Alpha-synuclein
摘要: The aggregation of proteins into oligomers and amyloid fibrils is characteristic several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process α-synuclein (α-syn) from monomers, via oligomeric intermediates, considered disease-causative toxic mechanism. We developed α-syn mutants that promote oligomer or fibril formation tested toxicity these by using a rat lentivirus system to investigate loss dopaminergic neurons in substantia nigra. most severe nigra observed animals with variants form (i.e., E57K E35K), whereas very quickly are less toxic. show vivo might interact potentially disrupt membranes.
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J. E. Galvin, K. Uryu, V. M.-Y. Lee, J. Q. Trojanowski, Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 13450- 13455 ,(1999) , 10.1073/PNAS.96.23.13450
Changyoun Kim, Seung‐Jae Lee, None, Controlling the mass action of α‐synuclein in Parkinson’s disease Journal of Neurochemistry. ,vol. 107, pp. 303- 316 ,(2008) , 10.1111/J.1471-4159.2008.05612.X
Juan J. Zarranz, Javier Alegre, Juan C. Gómez-Esteban, Elena Lezcano, Raquel Ros, Israel Ampuero, Lídice Vidal, Janet Hoenicka, Olga Rodriguez, Begoña Atarés, Verónica Llorens, Estrella Gomez Tortosa, Teodoro del Ser, David G. Muñoz, Justo G. de Yebenes, The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology. ,vol. 55, pp. 164- 173 ,(2004) , 10.1002/ANA.10795
K. M. Danzer, D. Haasen, A. R. Karow, S. Moussaud, M. Habeck, A. Giese, H. Kretzschmar, B. Hengerer, M. Kostka, Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding The Journal of Neuroscience. ,vol. 27, pp. 9220- 9232 ,(2007) , 10.1523/JNEUROSCI.2617-07.2007
Michel Goedert, Alpha-synuclein and neurodegenerative diseases. Nature Reviews Neuroscience. ,vol. 2, pp. 492- 501 ,(2001) , 10.1038/35081564
Damla Pinar Karpinar, Madhu Babu Gajula Balija, Sebastian Kügler, Felipe Opazo, Nasrollah Rezaei-Ghaleh, Nora Wender, Hai-Young Kim, Grit Taschenberger, Björn H Falkenburger, Henrike Heise, Ashutosh Kumar, Dietmar Riedel, Lars Fichtner, Aaron Voigt, Gerhard H Braus, Karin Giller, Stefan Becker, Alf Herzig, Marc Baldus, Herbert Jäckle, Stefan Eimer, Jörg B Schulz, Christian Griesinger, Markus Zweckstetter, Pre‐fibrillar α‐synuclein variants with impaired β‐structure increase neurotoxicity in Parkinson's disease models The EMBO Journal. ,vol. 28, pp. 3256- 3268 ,(2009) , 10.1038/EMBOJ.2009.257
Kelly A. Conway, James D. Harper, Peter T. Lansbury, Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nature Medicine. ,vol. 4, pp. 1318- 1320 ,(1998) , 10.1038/3311
J. B. Koprich, H. Siddiqi, O. Isacson, C. Y. Chung, Dynamic Changes in Presynaptic and Axonal Transport Proteins Combined with Striatal Neuroinflammation Precede Dopaminergic Neuronal Loss in a Rat Model of AAV α-Synucleinopathy The Journal of Neuroscience. ,vol. 29, pp. 3365- 3373 ,(2009) , 10.1523/JNEUROSCI.5427-08.2009
H. Heise, W. Hoyer, S. Becker, O. C. Andronesi, D. Riedel, M. Baldus, Molecular-level secondary structure, polymorphism, and dynamics of full-length ¿-synuclein fibrils studied by solid-state NMR Proceedings of the National Academy of Sciences of the United States of America. ,vol. 102, pp. 15871- 15876 ,(2005) , 10.1073/PNAS.0506109102
Hilal A. Lashuel, Dean Hartley, Benjamin M. Petre, Thomas Walz, Peter T. Lansbury, Amyloid pores from pathogenic mutations Nature. ,vol. 418, pp. 291- 291 ,(2002) , 10.1038/418291A