Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis

被引：1251

作者：

Ling, Shuo-Chien ^{[1
,2
,3
]}

Polymenidou, Magdalini ^{[1
,3
]}

Cleveland, Don W. ^{[1
,2
,3
]}

机构：

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

[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

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

来源：

NEURON | 2013年 / 79卷 / 03期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; DNA-BINDING PROTEIN; HEXANUCLEOTIDE REPEAT EXPANSION; MOTOR-NEURON DEGENERATION; SPINAL MUSCULAR-ATROPHY; CELL-FREE FORMATION; PRION-LIKE DOMAINS; STRESS GRANULES; TRANSGENIC MICE;

D O I：

10.1016/j.neuron.2013.07.033

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Breakthrough discoveries identifying common genetic causes for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have transformed our view of these disorders. They share unexpectedly similar signatures, including dysregulation in common molecular players including TDP-43, FUS/TLS, ubiquilin-2, VCP, and expanded hexanucleotide repeats within the C9ORF72 gene. Dysfunction in RNA processing and protein homeostasis is an emerging theme. We present the case here that these two processes are intimately linked, with disease-initiated perturbation of either leading to further deviation of both protein and RNA homeostasis through a feedforward loop including cell-to-cell prion-like spread that may represent the mechanism for relentless disease progression.

引用

页码：416 / 438

页数：23

共 253 条

[1] p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS [J].

Al-Sarraj, Safa ;

King, Andrew ;

Troakes, Claire ;

Smith, Bradley ;

Maekawa, Satomi ;

Bodi, Istvan ;

Rogelj, Boris ;

Al-Chalabi, Ammar ;

Hortobagyi, Tibor ;

Shaw, Christopher E. .

ACTA NEUROPATHOLOGICA, 2011, 122 (06) :691-702

[2] RNA granules: post-transcriptional and epigenetic modulators of gene expression [J].

Anderson, Paul ;

Kedersha, Nancy .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (06) :430-436

[3] The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response [J].

Andersson, Mattias K. ;

Stahlberg, Anders ;

Arvidsson, Yvonne ;

Olofsson, Anita ;

Semb, Henrik ;

Stenman, Goran ;

Nilsson, Ola ;

Aman, Pierre .

BMC CELL BIOLOGY, 2008, 9 (1)

[4] TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis [J].

Arai, Tetsuaki ;

Hasegawa, Masato ;

Akiyama, Haruhiko ;

Ikeda, Kenji ;

Nonaka, Takashi ;

Mori, Hiroshi ;

Mann, David ;

Tsuchiya, Kuniaki ;

Yoshida, Marl ;

Hashizume, Yoshio ;

Oda, Tatsuro .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 351 (03) :602-611

[5] ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43 [J].

Arnold, Eveline S. ;

Ling, Shuo-Chien ;

Huelga, Stephanie C. ;

Lagier-Tourenne, Clotilde ;

Polymenidou, Magdalini ;

Ditsworth, Dara ;

Kordasiewicz, Holly B. ;

McAlonis-Downes, Melissa ;

Platoshyn, Oleksandr ;

Parone, Philippe A. ;

Da Cruz, Sandrine ;

Clutario, Kevin M. ;

Swing, Debbie ;

Tessarollo, Lino ;

Marsala, Martin ;

Shaw, Christopher E. ;

Yeo, Gene W. ;

Cleveland, Don W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (08) :E736-E745

[6] Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS [J].

Ash, Peter E. A. ;

Bieniek, Kevin F. ;

Gendron, Tania F. ;

Caulfield, Thomas ;

Lin, Wen-Lang ;

DeJesus-Hernandez, Mariely ;

van Blitterswijk, Marka M. ;

Jansen-West, Karen ;

Paul, Joseph W., III ;

Rademakers, Rosa ;

Boylan, Kevin B. ;

Dickson, Dennis W. ;

Petrucelli, Leonard .

NEURON, 2013, 77 (04) :639-646

[7] Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection [J].

Avendano-Vazquez, S. Erendira ;

Dhir, Ashish ;

Bembich, Sara ;

Buratti, Emanuele ;

Proudfoot, Nicholas ;

Baralle, Francisco E. .

GENES & DEVELOPMENT, 2012, 26 (15) :1679-1684

[8] Cell stress induces TDP-43 pathological changes associated with ERK1/2 dysfunction: implications in ALS [J].

Ayala, Victoria ;

Belen Granado-Serrano, Ana ;

Cacabelos, Daniel ;

Naudi, Alba ;

Ilieva, Ekaterina V. ;

Boada, Jordi ;

Caraballo-Miralles, Victor ;

Llado, Jeronia ;

Ferrer, Isidro ;

Pamplona, Reinald ;

Portero-Otin, Manuel .

ACTA NEUROPATHOLOGICA, 2011, 122 (03) :259-270

[9] Structural determinants of the cellular localization and shuttling of TDP-43 [J].

Ayala, Youhna M. ;

Zago, Paola ;

D'Ambrogio, Andrea ;

Xu, Ya-Fei ;

Petrucelli, Leonard ;

Buratti, Emanuele ;

Baralle, Francisco E. .

JOURNAL OF CELL SCIENCE, 2008, 121 (22) :3778-3785

[10] TDP-43 regulates its mRNA levels through a negative feedback loop [J].

Ayala, Youhna M. ;

De Conti, Laura ;

Avendano-Vazquez, S. Erendira ;

Dhir, Ashish ;

Romano, Maurizio ;

D'Ambrogio, Andrea ;

Tollervey, James ;

Ule, Jernej ;

Baralle, Marco ;

Buratti, Emanuele ;

Baralle, Francisco E. .

EMBO JOURNAL, 2011, 30 (02) :277-288

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