Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?
- 1Department of Clinical Laboratory, Tokyo Medical and Dental University, Tokyo, Japan
- 2Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan
- Correspondence to Professor T Yokota, Department of Neurology and Neurological Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-819, Japan; tak-yokota.nuro{at}tmd.ac.jp
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Contributors All of the authors made substantial contributions to the conception and design of this review article. The authors drafted the article together and revised it critically for important intellectual content. The version to be published was approved by all of the authors.
- Received 10 November 2011
- Revised 19 March 2012
- Accepted 20 March 2012
- Published Online First 27 April 2012
Abstract
Progressive accumulation of specific misfolded protein is a defining feature of amyotrophic lateral sclerosis (ALS), similarly seen in Alzheimer disease, Parkinson disease, Huntington disease and Creutzfeldt–Jakob disease. The intercellular transfer of inclusions made of tau, α-synuclein and huntingtin has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system. Evidence for such a prion-like propagation mechanism has now spread to the major misfolded proteins, superoxide dismutase 1 (SOD1) and the 43 kDa transactive response DNA binding protein (TDP-43), implicated in ALS. The focus in this review is on what is known about ALS progression in terms of clinical as well as molecular aspects. Furthermore, the concept of ‘propagation’ is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.
Footnotes
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Competing interests None.
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Provenance and peer review Commissioned; externally peer reviewed.
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