Alpha-synuclein propagation: New insights from animal models

被引：97
作者：
Dehay, Benjamin [1 ,2 ]
Vila, Miquel [3 ,4 ,5 ]
Bezard, Erwan [1 ,2 ]
Brundin, Patrik [6 ]
Kordower, Jeffrey H. [7 ]
机构：
[1] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, F-33076 Bordeaux, France
[2] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France
[3] Vall dHebron Res Inst, Neurodegenerat Dis Res Grp, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
[4] Autonomous Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain
[5] Catalan Inst Res & Adv Studies, Barcelona, Spain
[6] Van Andel Res Inst, Ctr Neurodegenerat Sci, Lab Translat Parkinsons Dis Res, Grand Rapids, MI USA
[7] Rush Univ, Dept Neurol Sci, Grad Coll, Chicago, IL 60612 USA
来源：
MOVEMENT DISORDERS | 2016年 / 31卷 / 02期
关键词：
alpha-synuclein; propagation; synucleinopathy; Parkinson's disease; animal models; MULTIPLE SYSTEM ATROPHY; TO-NEURON TRANSMISSION; PARKINSONS-DISEASE; TRANSGENIC MICE; INCLUSION FORMATION; PATHOLOGY SPREAD; MUTATION; BRAIN; OLIGOMERS; FIBRILS;
D O I：
10.1002/mds.26370
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Aggregation of alpha-synuclein is implicated in several neurodegenerative diseases collectively termed synucleinopathies. Emerging evidence strongly implicates cell-to-cell transmission of misfolded alpha-synuclein as a common pathogenetic mechanism in synucleinopathies. The impact of alpha-synuclein pathology on neuronal dysfunction and behavioral impairments is being explored in animal models. This review provides an update on how research in animal models supports the concept that misfolded alpha-synuclein spreads from cell to cell and describes how findings in animal models might relate to the disease process in humans. Finally, we discuss the current underlying molecular and cellular mechanisms and future therapeutic strategies targeting alpha-synuclein propagation. (c) 2015 International Parkinson and Movement Disorder Society
引用
收藏
页码：161 / 168
页数：8
相关论文
共 66 条
[1]   Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission [J].
Alvarez-Erviti, Lydia ;
Seow, Yiqi ;
Schapira, Anthony H. ;
Gardiner, Chris ;
Sargent, Ian L. ;
Wood, Matthew J. A. ;
Cooper, J. Mark .
NEUROBIOLOGY OF DISEASE, 2011, 42 (03) :360-367
[2]   Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo [J].
Angot, Elodie ;
Steiner, Jennifer A. ;
Tome, Carla M. Lema ;
Ekstrom, Peter ;
Mattsson, Bengt ;
Bjorklund, Anders ;
Brundin, Patrik .
PLOS ONE, 2012, 7 (06)
[3]   Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease [J].
Appel-Cresswell, Silke ;
Vilarino-Guell, Carles ;
Encarnacion, Mary ;
Sherman, Holly ;
Yu, Irene ;
Shah, Brinda ;
Weir, David ;
Thompson, Christina ;
Szu-Tu, Chelsea ;
Trinh, Joanne ;
Aasly, Jan O. ;
Rajput, Alex ;
Rajput, Ali H. ;
Stoessl, A. Jon ;
Farrer, Matthew J. .
MOVEMENT DISORDERS, 2013, 28 (06) :811-813
[4]   Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases [J].
Bodner, RA ;
Outeiro, TF ;
Altmann, S ;
Maxwell, MM ;
Cho, SH ;
Hyman, BT ;
McLean, PJ ;
Young, AB ;
Housman, DE ;
Kazantsev, AG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (11) :4246-4251
[5]   Staging of brain pathology related to sporadic Parkinson's disease [J].
Braak, H ;
Del Tredici, K ;
Rüb, U ;
de Vos, RAI ;
Steur, ENHJ ;
Braak, E .
NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211
[6]   Research in motion: the enigma of Parkinson's disease pathology spread [J].
Brundin, Patrik ;
Li, Jia-Yi ;
Holton, Janice L. ;
Lindvall, Olle ;
Revesz, Tamas .
NATURE REVIEWS NEUROSCIENCE, 2008, 9 (10) :741-745
[7]   α-synuclein locus duplication as a cause of familial Parkinson's disease [J].
Chartier-Harlin, MC ;
Kachergus, J ;
Roumier, C ;
Mouroux, V ;
Douay, X ;
Lincoln, S ;
Levecque, C ;
Larvor, L ;
Andrieux, J ;
Hulihan, M ;
Waucquier, N ;
Defebvre, L ;
Amouyel, P ;
Farrer, M ;
Destée, A .
LANCET, 2004, 364 (9440) :1167-1169
[8]   Exosomal cell-to-cell transmission of alpha synuclein oligomers [J].
Danzer, Karin M. ;
Kranich, Lisa R. ;
Ruf, Wolfgang P. ;
Cagsal-Getkin, Ozge ;
Winslow, Ashley R. ;
Zhu, Liya ;
Vanderburg, Charles R. ;
McLean, Pamela J. .
MOLECULAR NEURODEGENERATION, 2012, 7
[9]   Heat-shock protein 70 modulates toxic extracellular α-synuclein oligomers and rescues trans-synaptic toxicity [J].
Danzer, Karin M. ;
Ruf, Wolfgang P. ;
Putcha, Preeti ;
Joyner, Daniel ;
Hashimoto, Tadafumi ;
Glabe, Charles ;
Hyman, Bradley T. ;
McLean, Pamela J. .
FASEB JOURNAL, 2011, 25 (01) :326-336
[10]   Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations [J].
Dehay, Benjamin ;
Bourdenx, Mathieu ;
Gorry, Philippe ;
Przedborski, Serge ;
Vila, Miquel ;
Hunot, Stephane ;
Singleton, Andrew ;
Olanow, C. Warren ;
Merchant, Kalpana M. ;
Bezard, Erwan ;
Petsko, Gregory A. ;
Meissner, Wassilios G. .
LANCET NEUROLOGY, 2015, 14 (08) :855-866
1234567