TY - JOUR T1 - Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation? JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 739 LP - 745 DO - 10.1136/jnnp-2011-301826 VL - 83 IS - 7 AU - Tadashi Kanouchi AU - Takuya Ohkubo AU - Takanori Yokota Y1 - 2012/07/01 UR - http://jnnp.bmj.com/content/83/7/739.abstract N2 - 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. ER -