Amyotrophic Lateral Sclerosis


Amyotrophic lateral sclerosis is a progressive neurodegenerative syndrome characterized by loss of motor neurons. Cognitive impairment occurs in a significant proportion of those affected. Numerous theories of pathogenesis have been advanced. The most cogent hypothesis is that genetic susceptibilities to neurodegeneration interact with environmental exposures, leading to neuronal injury, glial activation and neuronal death. Modern tools of molecular and cell biology and constructive international collaborations have provided insights into the factors that increase disease susceptibility. The important observation that genes associated with ribonucleic acid (RNA) processing are implicated in disease pathogenesis will undoubtedly influence the direction of research in the coming years. These factors, combined with improvements in clinical trial design, and an improved understanding of the limitations of translating positive findings from animal models to human subjects, are likely to lead to new and successful therapeutic options for patients in the near future.

Key concepts:

  • Amyotrophic lateral sclerosis is a motor system degeneration.

  • The incidence of amyotrophic lateral sclerosis is relatively uniform in populations of European ancestry. Disease frequency is lower in populations of mixed ancestry.

  • Amyotrophic lateral sclerosis (ALS) is associated with cognitive decline in up to 50% of cases, and with dementia in up to 20%. There is an acknowledged clinical, imaging, neuropathologic and neurogenetic overlap between ALS and frontotemporal dementia.

  • Amyotrophic lateral sclerosis is a complex genetic condition, in which genetic susceptibility interacts with environmental exposures to produce a neurodegenerative cascade.

  • The progression of amyotrophic lateral sclerosis is due in part to the activation of glia, which contributes to the process of neurodegeneration.

  • Recent genetic studies of amyotrophic lateral sclerosis have implicated genes involving RNA regulation, including transcription, RNA splicing, RNA transport and translation.

Keywords: motor neuron; neurodegeneration; frontotemporal dementia; complex genetics; superoxide dismutase; epidemiology

Further Reading

Andersen PM, Borasio GD, Dengler R et al. (2007) EALSC working group. Good practice in the management of amyotrophic lateral sclerosis: clinical guidelines. An evidence‐based review with good practice points. EALSC working group. Amyotrophic Lateral Sclerosis 8(4): 195–213. Review. PubMed PMID: 17653917.

Beleza‐Meireles A and Al‐Chalabi A (2009) Genetic studies of amyotrophic lateral sclerosis: controversies and perspectives. Amyotrophic Lateral Sclerosis 10(1): 1–14. PubMed PMID: 1911098.

Cronin S, Hardiman O and Traynor BJ (2007) Ethnic variation in the incidence of ALS: a systematic review. Neurology 68(13): 1002–1007. Review. PubMed PMID: 17389304.

Lagier‐Tourenne C and Cleveland DW (2009) Rethinking ALS: the FUS about TDP‐43. Cell 136(6): 1001–1004. Review. PubMed PMID: 19303844.

Lanka V and Cudkowicz M (2008) Therapy development for ALS: lessons learned and path forward. Amyotrophic Lateral Sclerosis 9(3): 131–140. Review. PubMed PMID: 18574756.

Logroscino G, Traynor BJ and Hardiman O (2009) Incidence of amyotrophic lateral sclerosis in Europe. Journal of Neurology, Neurosurgery, and Psychiatry. [Epub ahead of print] PubMed PMID: 19710046.

Phukan J, Pender NP and Hardiman O (2007) Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurology 6(11): 994–1003. Review. PubMed PMID: 17945153.

Rothstein JD (2009) Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Annals of Neurology 65(1): S3–S9. Review. PubMed PMID: 19191304.

Zaldivar T, Gutierrez J, Lara G et al. (2009) Reduced frequency of ALS in an ethnically mixed population: a population‐based mortality study. Neurology 72(19): 1640–1645. PubMed PMID: 19433736.

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How to Cite close
Hardiman, Orla(Feb 2010) Amyotrophic Lateral Sclerosis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000014.pub2]