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Current hypotheses for the underlying biology of amyotrophic lateral sclerosis

Rothstein, Jeffrey D.·2009·Annals of Neurology
DOI 10.1002/ana.21543
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Abstract

The mechanisms involved in selective motor neuron degeneration in amyotrophic lateral sclerosis remain unknown more than 135 years after the disease was first described. Although most cases have no known cause, mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) have been implicated in a fraction of familial cases of the disease. Transgenic mouse models with mutations in the SOD1 gene and other ALS genes develop pathology reminiscent of the disorder, including progressive death of motor neurons, and have provided insight into the pathogenesis of the disease but have consistently failed to predict therapeutic efficacy in humans. However, emerging research has demonstrated that mutations and pathology associated with the TDP‐43 gene and protein may be more common than SOD1 mutations in familial and sporadic ALS. Putative mechanisms of toxicity targeting motor neurons include oxidative damage, accumulation of intracellular aggregates, mitochondrial dysfunction, defects in axonal transport, growth factor deficiency, aberrant RNA metabolism, glial cell pathology, and glutamate excitotoxicity. Convergence of these pathways is likely to mediate disease onset and progression. Ann Neurol 2009;65 (suppl):S3–S9

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  • ALS is a fatal, adult-onset neurodegenerative disease in which motor neurons are selectively lost.

    “Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disease in which motor neurons (MNs) are selec-tively lost.”

    From MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models (2017) · cites this paper as Rothstein, 2009

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Authors
Rothstein, J. D.
Venue
Annals of Neurology
Publisher
Wiley
Published
2009-01
Volume
65
Issue
S1
ISSN
  • 0364-5134
  • 1531-8249
DOI
10.1002/ana.21543
Cited by
510
References
3
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 33 d)

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