TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

被引：2029

作者：

Sreedharan, Jemeen ^{[1
,2
]}

Blair, Ian P. ^{[4
,5
]}

Tripathi, Vineeta B. ^{[1
,2
]}

Hu, Xun ^{[1
,2
]}

Vance, Caroline ^{[1
,2
]}

Rogelj, Boris ^{[1
,2
]}

Ackerley, Steven ^{[1
,2
,3
]}

Durnall, Jennifer C. ^{[4
]}

Williams, Kelly L. ^{[4
]}

Buratti, Emanuele ^{[6
]}

Baralle, Francisco ^{[6
]}

de Belleroche, Jacqueline ^{[7
,8
]}

Mitchell, J. Douglas ^{[9
]}

Leigh, P. Nigel ^{[1
,2
]}

Al-Chalabi, Ammar ^{[1
,2
]}

Miller, Christopher C. ^{[1
,2
,3
]}

Nicholson, Garth ^{[4
,5
,10
]}

Shaw, Christopher E. ^{[1
,2
]}

机构：

[1] Kings Coll London, MRC Ctr Neurodegenerat Res, Dept Clin Neurosci, London SE5 8AF, England

[2] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England

[3] Kings Coll London, Dept Neurosci, MRC Ctr Neurodegenerat Res, London SE5 8AF, England

[4] ANZAC Res Inst, Northcott Neurosci Lab, Concord, NSW 2137, Australia

[5] Univ Sydney, Fac Med, Sydney, NSW 2139, Australia

[6] Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy

[7] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, Fac Med, London W6 8RF, England

[8] Charing Cross Hosp, London W6 8RF, England

[9] Royal Preston Hosp, Dept Neurol, Preston PR2 9HT, Lancs, England

[10] Concord Repatriat Gen Hosp, Mol Med Lab, Concord, NSW 2139, Australia

来源：

SCIENCE | 2008年 / 319卷 / 5870期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1126/science.1154584

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 fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein ( TDP- 43) inclusions. The function of TDP- 43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBP(M337V) segregated with disease within one kindred and a genome- wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP- 43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP- 43 and ALS.

引用

页码：1668 / 1672

页数：5

共 26 条

[1] A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues [J].

Abhyankar, Mayuresh M. ;

Urekar, Craig ;

Reddi, Prabhakara P. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (50) :36143-36154

[2] TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease [J].

Amador-Ortiz, Catalina ;

Lin, Wen-Lang ;

Ahmed, Zeshan ;

Personett, David ;

Davies, Peter ;

Dara, Ranjan ;

Graff-Radford, Neill R. ;

Hutton, Michael L. ;

Dickson, Dennis W. .

ANNALS OF NEUROLOGY, 2007, 61 (05) :435-445

[3] 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

[4] El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis [J].

Brooks, BR ;

Miller, RG ;

Swash, M ;

Munsat, TL .

AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS, 2000, 1 (05) :293-299

[5] TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail - An important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing [J].

Buratti, E ;

Brindisi, A ;

Giombi, M ;

Tisminetzky, S ;

Ayala, YM ;

Baralle, FE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (45) :37572-37584

[6] Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease [J].

Buratti, Emanuele ;

Baralle, Francisco E. .

FRONTIERS IN BIOSCIENCE-LANDMARK, 2008, 13 :867-878

[7] TAR-DNA binding protein 43 in Pick disease [J].

Freeman, Stefanie H. ;

Spires-Jones, Tara ;

Hyman, Bradley T. ;

Growdon, John H. ;

Frosch, Matthew P. .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2008, 67 (01) :62-67

[8]

GIJSELINCK I, 2007, IN PRESS NEUROBIOL A

[9] MOTOR-NEURON DEGENERATION IN MICE THAT EXPRESS A HUMAN CU,ZN SUPEROXIDE-DISMUTASE MUTATION [J].

GURNEY, ME ;

PU, HF ;

CHIU, AY ;

DALCANTO, MC ;

POLCHOW, CY ;

ALEXANDER, DD ;

CALIENDO, J ;

HENTATI, A ;

KWON, YW ;

DENG, HX ;

CHEN, WJ ;

ZHAI, P ;

SUFIT, RL ;

SIDDIQUE, T .

SCIENCE, 1994, 264 (5166) :1772-1775

[10] A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2 [J].

Hadano, S ;

Hand, CK ;

Osuga, H ;

Yanagisawa, Y ;

Otomo, A ;

Devon, RS ;

Miyamoto, N ;

Showguchi-Miyata, J ;

Okada, Y ;

Singaraja, R ;

Figlewicz, DA ;

Kwiatkowski, T ;

Hosler, BA ;

Sagie, T ;

Skaug, J ;

Nasir, J ;

Brown, RH ;

Scherer, SW ;

Rouleau, GA ;

Hayden, MR ;

Ikeda, JE .

NATURE GENETICS, 2001, 29 (02) :166-173

← 1 2 3 →