Prion-like Properties of Misfolded Cu/Zn-superoxide Dismutase in Amyotrophic Lateral Sclerosis: Update and Perspectives

Eiichi Tokuda, Stefan L. Marklund, Yoshiaki Furukawa

Research output: Contribution to journalArticle

1 Citation (Scopus)


Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that is characterized by the loss of motor neurons, which results in progressive muscle atrophy. The pathology spreads from the initial site of onset to contiguous anatomic regions. Mutations in the gene encoding Cu/Zn-superoxide dismutase (SOD1) have been identified in a dominantly inherited form of ALS (ALS-SOD1). A major hallmark of ALS-SOD1 is the abnormal accumulation of conformationally aberrant SOD1 protein (i.e., misfolded SOD1) within motor neurons. Emerging experimental evidence has suggested that misfolded proteins associated with neurodegenerative diseases exhibit prion-like properties, i.e., misfolded proteins act as conformational templates that convert normal proteins into a pathogenic form. Possibly as a result of this prion-like self-propagation property, misfolded forms of pathological proteins are considered to accumulate in the central nervous system and cause neurodegeneration. In this article, we review recent evidence for the role of prion-like mechanisms in ALS-SOD1. In particular, we discuss the propensity of misfolded SOD1 to act as a pathological seed, spread between cells, and propagate neuroanatomically.

Original languageEnglish
Pages (from-to)1015-1019
Number of pages5
JournalYakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Issue number7
Publication statusPublished - 2019 Jan 1



  • amyotrophic lateral sclerosis
  • prion-like propagation
  • superoxide dismutase-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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