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Amyotrophic lateral sclerosis

About: Amyotrophic lateral sclerosis is a research topic. Over the lifetime, 12011 publications have been published within this topic receiving 494642 citations. The topic is also known as: ALS & Lou Gehrig's disease.


Papers
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Journal ArticleDOI
01 Feb 1997-Neuron
TL;DR: It is reported here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity.

1,343 citations

Journal ArticleDOI
TL;DR: The creation and characterization of mice completely deficient for SOD1 indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.
Abstract: The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD-deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.

1,305 citations

Journal ArticleDOI
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.
Abstract: Considerable progress has been made in unraveling the genetic etiology of amyotrophic lateral sclerosis (ALS), the most common form of adult-onset motor neuron disease and the third most common neurodegenerative disease overall. Here we review genes implicated in the pathogenesis of motor neuron degeneration and how this new information is changing the way we think about this fatal disorder. Specifically, we summarize current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1, and evaluate the information being gleaned from genome-wide association studies. We also outline emerging themes in ALS research, such as next-generation sequencing approaches to identify de novo mutations, the genetic convergence of familial and sporadic ALS, the proposed oligogenic basis for the disease, and how each new genetic discovery is broadening the phenotype associated with the clinical entity we know as ALS.

1,298 citations

Journal ArticleDOI
TL;DR: It is concluded that in this widely studied animal model of human ALS, and in this single human case, motor neuron pathology begins at the distal axon and proceeds in a "dying back" pattern.

1,239 citations

Journal ArticleDOI
18 Sep 1998-Science
TL;DR: Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties, raising the question of whether toxicity arises from superoxide-mediated oxidative stress.
Abstract: Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.

1,198 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
20231,020
20222,609
2021728
2020704
2019651