Protein aggregates and regional disease spread in ALS is reminiscent of prion-like pathogenesis

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8 Scopus citations


Amyotrophic lateral sclerosis (ALS) typically commences in a discrete location in a limb or bulbar territory muscles and then spreads to the adjacent anatomical regions. This pattern is consistent with a contiguous spread of the disease process in motor neuron network resulting in progressive motor weakness. The etiology of ALS onset and the mechanism of the regional ALS spread remain elusive. Over the past 5 years, identification of mutations in two RNA binding proteins, trans active response (TAR) DNA-binding protein (TDP-43) and fused in sarcoma (FUS), in patients with familial ALS has led to a major shift in our understanding of the ALS disease mechanism. In addition to their role in RNA metabolism, TDP-43 and FUS form protein aggregates in the affected neurons. More recent findings demonstrating that both TDP-43 and FUS contain glutamine/asparagine (Q/N) residue-rich prion-like domains have spurred intense research interest. This brief review discusses the prion-related domains in TDP-43 and FUS and their implication in protein aggregate formation and disease spread in ALS.

Original languageEnglish (US)
Pages (from-to)107-110
Number of pages4
JournalNeurology India
Issue number2
StatePublished - Mar 1 2013


  • Aggregates
  • ALS
  • FUS
  • Prion
  • Q/N domain
  • TDP-43

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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