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

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