Decoding ALS: from genes to mechanism

被引：1484

作者：

Taylor, J. Paul ^{[1
,2
]}

Brown, Robert H., Jr. ^{[3
]}

Cleveland, Don W. ^{[4
,5
]}

机构：

[1] St Jude Childrens Res Hosp, Howard Hughes Med Inst, 332 N Lauderdale St, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, 332 N Lauderdale St, Memphis, TN 38105 USA

[3] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA

[4] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

来源：

NATURE | 2016年 / 539卷 / 7628期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; DIPEPTIDE-REPEAT PROTEINS; FRONTOTEMPORAL LOBAR DEGENERATION; C9ORF72 HEXANUCLEOTIDE REPEAT; SUPEROXIDE-DISMUTASE GENE; PRION-LIKE PROPAGATION; RNA-BINDING PROTEINS; BAC TRANSGENIC MICE; FAMILIAL ALS;

D O I：

10.1038/nature20413

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors have been identified that drive the degeneration of motor neurons in ALS, increase susceptibility to the disease or influence the rate of its progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, the induction of stress at the endoplasmic reticulum and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through liquid-liquid phase separation. Extraordinary progress in understanding the biology of ALS provides new reasons for optimism that meaningful therapies will be identified.

引用

页码：197 / 206

页数：10

共 147 条

[21] MicroRNAs as Potential Circulating Biomarkers for Amyotrophic Lateral Sclerosis [J].

Cloutier, Frank ;

Marrero, Alier ;

O'Connell, Colleen ;

Morin, Pier, Jr. .

JOURNAL OF MOLECULAR NEUROSCIENCE, 2015, 56 (01) :102-112

[22] Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy [J].

Cooper-Knock, Johnathan ;

Higginbottom, Adrian ;

Stopford, Matthew J. ;

Highley, J. Robin ;

Ince, Paul G. ;

Wharton, Stephen B. ;

Pickering-Brown, Stuart ;

Kirby, Janine ;

Hautbergue, Guillaume M. ;

Shaw, Pamela J. .

ACTA NEUROPATHOLOGICA, 2015, 130 (01) :63-75

[23] Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72 [J].

Cooper-Knock, Johnathan ;

Hewitt, Christopher ;

Highley, J. Robin ;

Brockington, Alice ;

Milano, Antonio ;

Man, Somai ;

Martindale, Joanne ;

Hartley, Judith ;

Walsh, Theresa ;

Gelsthorpe, Catherine ;

Baxter, Lynne ;

Forster, Gillian ;

Fox, Melanie ;

Bury, Joanna ;

Mok, Kin ;

McDermott, Christopher J. ;

Traynor, Bryan J. ;

Kirby, Janine ;

Wharton, Stephen B. ;

Ince, Paul G. ;

Hardy, John ;

Shaw, Pamela J. .

BRAIN, 2012, 135 :751-764

[24] Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS [J].

DeJesus-Hernandez, Mariely ;

Mackenzie, Ian R. ;

Boeve, Bradley F. ;

Boxer, Adam L. ;

Baker, Matt ;

Rutherford, Nicola J. ;

Nicholson, Alexandra M. ;

Finch, NiCole A. ;

Flynn, Heather ;

Adamson, Jennifer ;

Kouri, Naomi ;

Wojtas, Aleksandra ;

Sengdy, Pheth ;

Hsiung, Ging-Yuek R. ;

Karydas, Anna ;

Seeley, William W. ;

Josephs, Keith A. ;

Coppola, Giovanni ;

Geschwind, Daniel H. ;

Wszolek, Zbigniew K. ;

Feldman, Howard ;

Knopman, David S. ;

Petersen, Ronald C. ;

Miller, Bruce L. ;

Dickson, Dennis W. ;

Boylan, Kevin B. ;

Graff-Radford, Neill R. ;

Rademakers, Rosa .

NEURON, 2011, 72 (02) :245-256

[25] Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia [J].

Deng, Han-Xiang ;

Chen, Wenjie ;

Hong, Seong-Tshool ;

Boycott, Kym M. ;

Gorrie, George H. ;

Siddique, Nailah ;

Yang, Yi ;

Fecto, Faisal ;

Shi, Yong ;

Zhai, Hong ;

Jiang, Hujun ;

Hirano, Makito ;

Rampersaud, Evadnie ;

Jansen, Gerard H. ;

Donkervoort, Sandra ;

Bigio, Eileen H. ;

Brooks, Benjamin R. ;

Ajroud, Kaouther ;

Sufit, Robert L. ;

Haines, Jonathan L. ;

Mugnaini, Enrico ;

Pericak-Vance, Margaret A. ;

Siddique, Teepu .

NATURE, 2011, 477 (7363) :211-U113

[26] Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria [J].

Deng, HX ;

Shi, Y ;

Furukawa, Y ;

Zhai, H ;

Fu, RG ;

Liu, ED ;

Gorrie, GH ;

Khan, MS ;

Hung, WY ;

Bigio, EH ;

Lukas, T ;

Dal Canto, MC ;

O'Halloran, TV ;

Siddique, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (18) :7142-7147

[27] Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model [J].

Di Giorgio, Francesco Paolo ;

Carrasco, Monica A. ;

Siao, Michelle C. ;

Maniatis, Tom ;

Eggan, Kevin .

NATURE NEUROSCIENCE, 2007, 10 (05) :608-614

[28] RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention [J].

Donnelly, Christopher J. ;

Zhang, Ping-Wu ;

Pham, Jacqueline T. ;

Heusler, Aaron R. ;

Mistry, Nipun A. ;

Vidensky, Svetlana ;

Daley, Elizabeth L. ;

Poth, Erin M. ;

Hoover, Benjamin ;

Fines, Daniel M. ;

Maragakis, Nicholas ;

Tienari, Pentti J. ;

Petrucelli, Leonard ;

Traynor, Bryan J. ;

Wang, Jiou ;

Rigo, Frank ;

Bennett, C. Frank ;

Blackshaw, Seth ;

Sattler, Rita ;

Rothstein, Jeffrey D. .

NEURON, 2013, 80 (02) :415-428

[29] Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS [J].

Elden, Andrew C. ;

Kim, Hyung-Jun ;

Hart, Michael P. ;

Chen-Plotkin, Alice S. ;

Johnson, Brian S. ;

Fang, Xiaodong ;

Armakola, Maria ;

Geser, Felix ;

Greene, Robert ;

Lu, Min Min ;

Padmanabhan, Arun ;

Clay-Falcone, Dana ;

McCluskey, Leo ;

Elman, Lauren ;

Juhr, Denise ;

Gruber, Peter J. ;

Rueb, Udo ;

Auburger, Georg ;

Trojanowski, John Q. ;

Lee, Virginia M. -Y. ;

Van Deerlin, Vivianna M. ;

Bonini, Nancy M. ;

Gitler, Aaron D. .

NATURE, 2010, 466 (7310) :1069-U77

[30] Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: a new mechanism for ALS [J].

Emde, Anna ;

Eitan, Chen ;

Liou, Lee-Loung ;

Libby, Ryan T. ;

Rivkin, Natali ;

Magen, Iddo ;

Reichenstein, Irit ;

Oppenheim, Hagar ;

Eilam, Raya ;

Silvestroni, Aurelio ;

Alajajian, Betty ;

Ben-Dov, Iddo Z. ;

Aebischer, Julianne ;

Savidor, Alon ;

Levin, Yishai ;

Sons, Robert ;

Hammond, Scott M. ;

Ravits, John M. ;

Moeller, Thomas ;

Hornstein, Eran .

EMBO JOURNAL, 2015, 34 (21) :2633-2651

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