Pathogenic superoxide dismutase structure, folding, aggregation and turnover

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Significant advances have been made during the past two years toward an understanding of the molecular basis for how mutations in human cytosolic copper-zinc superoxide dismutase (SOD1) cause the inherited form of amyotrophic lateral sclerosis (ALS). Biophysical studies suggest that the pathogenic mutations destabilize loop or β-barrel structural elements of the protein. With few exceptions, the loss of metal ions and reduction of the intrasubunit disulfide bond enhance this destabilization. In mouse models of the disease, the formation of visible aggregates containing mutant SOD1 occurs relatively late in the lifespan, hinting that the quality control and protein turnover systems of motor neurons eventually become overwhelmed or compromised. Studies probing SOD1 turnover have suggested the possibility that proteolytic breakdown products may play a role in pathogenesis.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalCurrent Opinion in Chemical Biology
Volume10
Issue number2
DOIs
StatePublished - Apr 2006

Fingerprint

Superoxide Dismutase
Agglomeration
Mutation
Amyotrophic Lateral Sclerosis
Motor Neurons
Disulfides
Quality Control
Neurons
Quality control
Metal ions
Zinc
Copper
Proteins
Metals
Ions
Protein Structural Elements

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pathogenic superoxide dismutase structure, folding, aggregation and turnover. / Hart, P. John.

In: Current Opinion in Chemical Biology, Vol. 10, No. 2, 04.2006, p. 131-138.

Research output: Contribution to journalArticle

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