Parkinson's Disease and α-Synuclein Expression

被引:141
作者
Devine, Michael J. [1 ]
Gwinn, Katrina [2 ]
Singleton, Andrew [3 ]
Hardy, John [1 ]
机构
[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
[2] Baylor Coll Med, Houston, TX 77030 USA
[3] NIA, NIH, Bethesda, MD 20892 USA
基金
英国医学研究理事会; 英国惠康基金;
关键词
Parkinsonism; genetics; alpha-synuclein; MULTIPLE SYSTEM ATROPHY; LEWY BODY; IN-VIVO; SNCA DUPLICATION; GENE DUPLICATION; MOUSE MODEL; NEURODEGENERATIVE DISEASE; DOPAMINERGIC-NEURONS; LOCUS TRIPLICATION; MESSENGER-RNA;
D O I
10.1002/mds.23948
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. alpha-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of alpha-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of alpha-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. (C) 2011 Movement Disorder Society
引用
收藏
页码:2160 / 2168
页数:9
相关论文
共 99 条
[51]   In vivo silencing of alpha-synuclein using naked siRNA [J].
Lewis, Jada ;
Melrose, Heather ;
Bumcrot, David ;
Hope, Andrew ;
Zehr, Cynthia ;
Lincoln, Sarah ;
Braithwaite, Adam ;
He, Zhen ;
Ogholikhan, Sina ;
Hinkle, Kelly ;
Kent, Caroline ;
Toudjarska, Ivanka ;
Charisse, Klaus ;
Braich, Ravi ;
Pandey, Rajendra K. ;
Heckman, Michael ;
Maraganore, Demetrius M. ;
Crook, Julia ;
Farrer, Matthew J. .
MOLECULAR NEURODEGENERATION, 2008, 3 (1)
[52]   Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation [J].
Li, Jia-Yi ;
Englund, Elisabet ;
Holton, Janice L. ;
Soulet, Denis ;
Hagell, Peter ;
Lees, Andrew J. ;
Lashley, Tammaryn ;
Quinn, Niall P. ;
Rehncrona, Stig ;
Bjorklund, Anders ;
Widner, Hakan ;
Revesz, Tamas ;
Lindvall, Olle ;
Brundin, Patrik .
NATURE MEDICINE, 2008, 14 (05) :501-503
[53]   α-Syn Suppression Reverses Synaptic and Memory Defects in a Mouse Model of Dementia with Lewy Bodies [J].
Lim, Youngshin ;
Kehm, Victoria M. ;
Lee, Edward B. ;
Soper, James H. ;
Li, Chi ;
Trojanowski, John Q. ;
Lee, Virginia M. -Y. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (27) :10076-10087
[54]   Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein [J].
Lin, Xian ;
Parisiadou, Loukia ;
Gu, Xing-Long ;
Wang, Lizhen ;
Shim, Hoon ;
Sun, Lixin ;
Xie, Chengsong ;
Long, Cai-Xia ;
Yang, Wan-Jou ;
Ding, Jinhui ;
Chen, Zsu Zsu ;
Gallant, Paul E. ;
Tao-Cheng, Jung-Hwa ;
Rudow, Gay ;
Troncoso, Juan C. ;
Liu, Zhihua ;
Li, Zheng ;
Cai, Huaibin .
NEURON, 2009, 64 (06) :807-827
[55]   Genetic Regulation of α-Synuclein mRNA Expression in Various Human Brain Tissues [J].
Linnertz, Colton ;
Saucier, Laura ;
Ge, Dongliang ;
Cronin, Kenneth D. ;
Burke, James R. ;
Browndyke, Jeffrey N. ;
Hulette, Christine M. ;
Welsh-Bohmer, Kathleen A. ;
Chiba-Falek, Ornit .
PLOS ONE, 2009, 4 (10)
[56]   α-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease [J].
Lo Bianco, C ;
Ridet, JL ;
Schneider, BL ;
Déglon, N ;
Aebischer, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10813-10818
[57]   The Transgenic Overexpression of α-Synuclein and Not Its Related Pathology Associates with Complex I Inhibition [J].
Loeb, Virginie ;
Yakunin, Eugenia ;
Saada, Ann ;
Sharon, Ronit .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (10) :7334-7343
[58]   Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease [J].
Maraganore, Demetrius M. ;
de Andrade, Mariza ;
Elbaz, Alexis ;
Farrer, Matthew J. ;
Ioannidis, John P.A. ;
Krueger, Rejko ;
Rocca, Walter A. ;
Schneider, Nicole K. ;
Lesnick, Timothy G. ;
Lincoln, Sarah J. ;
Hulihan, Mary M. ;
Aasly, Jan O. ;
Ashizawa, Tetsuo ;
Chartier-Harlin, Marie-Christine ;
Checkoway, Harvey ;
Ferrarese, Carlo ;
Hadjigeorgiou, Georgios ;
Hattori, Nobutaka ;
Kawakami, Hideshi ;
Lambert, Jean-Charles ;
Lynch, Timothy ;
Mellick, George D. ;
Papapetropoulos, Spiridon ;
Parsian, Abbas ;
Quattrone, Aldo ;
Riess, Olaf ;
Tan, Eng-King ;
Van Broeckhoven, Christine .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (06) :661-670
[59]  
MAROTEAUX L, 1988, J NEUROSCI, V8, P2804
[60]   Parkinson's disease α-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death [J].
Martin, LJ ;
Pan, Y ;
Price, AC ;
Sterling, W ;
Copeland, NG ;
Jenkins, NA ;
Price, DL ;
Lee, MK .
JOURNAL OF NEUROSCIENCE, 2006, 26 (01) :41-50