From Nucleation to Widespread Propagation: A Prion-Like Concept for ALS

Virus Res. 2015 Sep 2;207:94-105. doi: 10.1016/j.virusres.2014.12.032. Epub 2015 Feb 2.

Abstract

Propagation of pathological protein assemblies via a prion-like mechanism has been suggested to drive neurodegenerative diseases, such as Parkinson's and Alzheimer's. Recently, amyotrophic lateral sclerosis (ALS)-linked proteins, such as SOD1, TDP-43 and FUS were shown to follow self-perpetuating seeded aggregation, thereby adding ALS to the group of prion-like disorders. The cell-to-cell spread of these pathological protein assemblies and their pathogenic mechanism is poorly understood. However, as ALS is a non-cell autonomous disease and pathology in glial cells was shown to contribute to motor neuron damage, spreading mechanisms are likely to underlie disease progression via the interplay between affected neurons and their neighboring glial cells.

Keywords: ALS; C9orf72; FUS; Prion-like transmission; Stress granules; TDP-43.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / metabolism*
  • RNA-Binding Protein FUS / chemistry*
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism
  • Superoxide Dismutase / chemistry*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1

Substances

  • DNA-Binding Proteins
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1