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The role of RNA processing in the pathogenesis of motor neuron degeneration

  • Dirk Bäumer (a1) (a2), Olaf Ansorge (a3), Mara Almeida (a1) and Kevin Talbot (a1) (a2)

Abstract

Motor neurons are large, highly polarised cells with very long axons and a requirement for precise spatial and temporal gene expression. Neurodegenerative disorders characterised by selective motor neuron vulnerability include various forms of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). A rapid expansion in knowledge on the pathophysiology of motor neuron degeneration has occurred in recent years, largely through the identification of genes leading to familial forms of ALS and SMA. The major emerging theme is that motor neuron degeneration can result from mutation in genes that encode factors important for ribonucleoprotein biogenesis and RNA processing, including splicing regulation, transcript stabilisation, translational repression and localisation of mRNA. Complete understanding of how these pathways interact and elucidation of specialised mechanisms for mRNA targeting and processing in motor neurons are likely to produce new targets for therapy in ALS and related disorders.

Copyright

Corresponding author

*Corresponding author: Kevin Talbot, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK. E-mail: kevin.talbot@clneuro.ox.ac.uk

References

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Publications

There has been a wealth of recent interest in the topic of RNA-interacting proteins in neuronal degeneration. Several competing reviews have recently been published which treat the subject in a slightly different way to the current article, in which we have tried to provide an integrated view within the context of the cellular pathway of RNA-binding proteins in neurons. Kolb and colleagues review what is known about the function of the individual genes involved in motor system degenerations, while Strong provides some important insights into how RNA metabolism might integrate with axonal transport proteins. Neumann and colleagues focus on the pathogenesis of frontotemporal dementia and touch on its relationship with ALS.

Strong, M.J. (2010). The evidence for altered RNA metabolism in amyotrophic lateral sclerosis (ALS). Journal of the Neurological Sciences 288, 1-12
Kolb, S.J., Sutton, S. and Schoenberg, D.R. (2010). RNA processing defects associated with diseases of the motor neuron. Muscle and Nerve 41, 5-17
Neumann, M., Tolnay, M. and Mackenzie, I.R. (2009). The molecular basis of frontotemporal dementia. Expert Reviews in Molecular Medicine 11, e23

ALSOD is the Amyotrophic Lateral Sclerosis Online genetic Database. It is designed to provide both the scientific community and wider public with up-to-date information on ALS genetics.

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The role of RNA processing in the pathogenesis of motor neuron degeneration

  • Dirk Bäumer (a1) (a2), Olaf Ansorge (a3), Mara Almeida (a1) and Kevin Talbot (a1) (a2)

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