There is a glutamate-receptor defect in patients with amyotrophic lateral sclerosis.
Abstract
The aetiology of sporadic amyotrophic lateral sclerosis (ALS), a fatal paralytic disease, is largely unknown. Here we show that there is a defect in the editing of the messenger RNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by ALS. This failure to swap an arginine for a glutamine residue at a crucial site in the subunit, which occurs normally in the affected brain areas of patients with other neurodegenerative diseases, will interfere with the correct functioning of the glutamate receptors and may be a contributory cause of neuronal death in ALS patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
£199.00 per year
only £3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Sommer, B., Köhler, M., Sprengel, R. & Seeberg, P. Cell 67, 11–19 (1991).
Brusa, R. et al. Science 270, 1677–1680 (1995).
Higuchi, M. et al. Nature 406, 78–81 (2000).
Kawahara, Y. et al. J. Neurochem. 85, 680–689 (2003).
Takuma, H., Kwak, S., Yoshizawa, T. & Kanazawa, I. Ann. Neurol. 46, 806–815 (1999).
Kawahara, Y., Ito, K., Sun, H., Kanazawa, I. & Kwak, S. Eur. J. Neurosci. 18, 23–33 (2003).
Feldmeyer, D. et al. Nature Neurosci. 2, 57–64 (1999).
Greger, I. H., Khatri, L., Kong, X. & Ziff, E. B. Neuron 40, 763–774 (2003).
Akbarian, S., Smith, M. & Jones, E. Brain Res. 699, 297–304 (1995).
Lin, C. -L. G. et al. Neuron 20, 589–602 (1998).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
This contains supplementary methods and one supplementary table. (DOC 62 kb)
Rights and permissions
About this article
Cite this article
Kawahara, Y., Ito, K., Sun, H. et al. RNA editing and death of motor neurons. Nature 427, 801 (2004). https://doi.org/10.1038/427801a
Issue date:
DOI: https://doi.org/10.1038/427801a
This article is cited by
-
Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms
Molecular Neurodegeneration (2023)
-
The Fragile X Protein Family in Amyotrophic Lateral Sclerosis
Molecular Neurobiology (2023)
-
Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis
Journal of Neurology (2022)
-
Multi-phaseted problems of TDP-43 in selective neuronal vulnerability in ALS
Cellular and Molecular Life Sciences (2021)
-
Defining novel functions for cerebrospinal fluid in ALS pathophysiology
Acta Neuropathologica Communications (2020)