Journal ArticleDOI
Whole-Genome Analysis of Sporadic Amyotrophic Lateral Sclerosis
Travis Dunckley,Matthew J. Huentelman,David Craig,John V. Pearson,Szabolcs Szelinger,Keta Joshipura,Rebecca F. Halperin,Chelsea Stamper,Kendall Jensen,David Letizia,Sharon E. Hesterlee,Alan Pestronk,Todd Levine,Tulio E. Bertorini,Michael C. Graves,Tahseen Mozaffar,Carlayne E. Jackson,Peter Bosch,April McVey,Arthur Dick,Richard J. Barohn,Catherine Lomen-Hoerth,Jeffrey Rosenfeld,Daniel T. O'Connor,Kuixing Zhang,Richard Crook,Henrik Ryberg,Mike Hutton,Jonathan S. Katz,Ericka Simpson,Hiroshi Mitsumoto,Robert Bowser,Robert G. Miller,Stanley H. Appel,Dietrich A. Stephan +34 more
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TLDR
Variants of FLJ10986 may confer susceptibility to sporadic ALS and 50 other candidate loci warrant further investigation for their potential role in conferring susceptibility to the disease.Abstract:
Background Approximately 90% of persons with amyotrophic lateral sclerosis (ALS) have the sporadic form, which may be caused by the interaction of multiple environmental factors and previously unknown genes. Methods We performed a genomewide association analysis using 766,955 single-nucleotide polymorphisms (SNPs) found in 386 white patients with sporadic ALS and 542 neurologically normal white controls (the discovery series). Associations of SNPs with sporadic ALS were confirmed in two independent replication populations: replication series 1, with 766 case patients with the disease and 750 neurologically normal controls, and replication series 2, with 135 case patients and 275 controls. Results We identified 10 genetic loci that are significantly associated (P<0.05) with sporadic ALS in three independent series of case patients and controls and an additional 41 loci that had significant associations in two of the three series. The most significant association with disease in white case patients as compa...read more
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Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons.
John T. Dimos,Kit T. Rodolfa,Kathy K. Niakan,Laurin M. Weisenthal,Hiroshi Mitsumoto,Wendy K. Chung,Wendy K. Chung,Gist F. Croft,Genevieve Saphier,Rudy Leibel,Robin Goland,Hynek Wichterle,Christopher E. Henderson,Kevin Eggan +13 more
TL;DR: Induced pluripotent stem cells are generated from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
Journal ArticleDOI
State of play in amyotrophic lateral sclerosis genetics.
TL;DR: Current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1 are summarized and how each new genetic discovery is broadening the phenotype associated with the clinical entity the authors know as ALS is outlined.
Journal ArticleDOI
Blood-Brain Barrier: From Physiology to Disease and Back
TL;DR: This review examines molecular and cellular mechanisms underlying the establishment of the blood-brain barrier, and examines how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders.
Journal ArticleDOI
MicroRNA-206 Delays ALS Progression and Promotes Regeneration of Neuromuscular Synapses in Mice
Andrew H. Williams,Gregorio Valdez,Viviana Moresi,Xiaoxia Qi,John McAnally,Jeffrey L. Elliott,Rhonda Bassel-Duby,Joshua R. Sanes,Eric N. Olson +8 more
TL;DR: It is shown that a small noncoding RNA that is selectively expressed in skeletal muscle, miR-206, senses motor neuron injury or loss and helps ameliorate resultant muscle damage by promoting regeneration of neuromuscular synapses and slows disease progression in ALS.
Journal ArticleDOI
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
TL;DR: Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS.
References
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Journal ArticleDOI
El Escorial revisited : revised criteria for the diagnosis of amyotrophic lateral sclerosis
TL;DR: The criteria described below represent the result of a three-day workshop, convened at Airlie Conference Center, Warrenton, Virginia on 2–4 April, 1998 by the World Federation of Neurology Research Committee on Motor Neuron Diseases, and are placed on the WFN ALS website.
Journal ArticleDOI
Unraveling the mechanisms involved in motor neuron degeneration in ALS.
TL;DR: Along with errors in the handling of synaptic glutamate and the potential excitotoxic response this provokes, model systems highlight the involvement of nonneuronal cells in disease progression and provide new therapeutic strategies.
Journal ArticleDOI
From charcot to lou gehrig: deciphering selective motor neuron death in als
TL;DR: Insights into abnormalities in two genes, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.
Journal ArticleDOI
Molecular biology of amyotrophic lateral sclerosis: insights from genetics.
Piera Pasinelli,Robert H. Brown +1 more
TL;DR: An overview of the mechanisms for motor neuron death and the role of non-neuronal cells in ALS is presented and new insights are generated into the diverse molecular pathways involved in ALS pathogenesis.
Journal ArticleDOI
From genotypes to genes: doubling the sample size.
TL;DR: This paper considers the analysis of genetic case-control data and recommends that analyses that treat alleles rather than people as observations should not be used, and that such data should be analyzed by genotype.
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