Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?

• Published in: Journal of Neurology, Neurosurgery and Psychiatry Vol. 83; no. 7; pp. 739 - 745
• Main Authors: Kanouchi, Tadashi, Ohkubo, Takuya, Yokota, Takanori
• Format: Journal Article Book Review
• Language: English
• Published: London BMJ Publishing Group Ltd 01.07.2012; BMJ Publishing Group; BMJ Publishing Group LTD; BMJ Group
• Series: Review
• Subjects: Amyotrophic Lateral Sclerosis - etiology; Amyotrophic Lateral Sclerosis - pathology; Biological and medical sciences; Disease Progression; DNA-Binding Proteins - physiology; Humans; Medical sciences; Motor Neurons - physiology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurodegeneration; Neurology; Prions - physiology; Superoxide Dismutase - physiology; Superoxide Dismutase-1; Nervous system diseases; Propagation; Motor system disorder; Central nervous system disease; Amyotrophic lateral sclerosis; Degenerative disease; Prion; Neurological disorder; Spinal cord disease
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2011-301826

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.