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Prions and manganese: A maddening beast

David R Brown1

  • 1Department of Biology and Biochemistry, University of Bath, Bath, UKBA2 7AY. bssdrb@bath.ac.uk

Metallomics : Integrated Biometal Science
|March 11, 2011
PubMed

Insights

Manganese may play a crucial role in prion diseases, potentially stabilizing prions and offering therapeutic targets. Chelation therapy targeting manganese shows promise in extending lifespan in affected animals.

Area of Science:

  • Neurodegenerative diseases
  • Prion biology
  • Metal-protein interactions

Background:

  • Prion diseases, such as variant Creutzfeldt-Jakob disease (vCJD), are transmissible neurodegenerative disorders.
  • The prion protein (PrP) is known for its association with these diseases and its role as a copper-binding protein.
  • The interaction of PrP with other metals, particularly manganese (Mn), has been historically underestimated compared to copper.

Purpose of the Study:

  • To review the existing evidence linking manganese to prion diseases.
  • To highlight the emerging role of manganese in prion stabilization and disease progression.
  • To explore the therapeutic potential of targeting manganese in prion disease treatment.

Main Methods:

  • Literature review of studies investigating the PrP-manganese interaction.
  • Analysis of data on manganese's effect on prion stability in the environment.
  • Examination of results from chelation therapy trials targeting manganese in animal models.

Main Results:

  • Recent findings suggest manganese can stabilize prions, potentially contributing to their environmental persistence.
  • Chelation therapy specifically targeting manganese has demonstrated an ability to extend survival times in animal models of prion disease.
  • The historical underestimation of the manganese-prion link is being challenged by new data.

Conclusions:

  • Manganese represents a significant, yet underappreciated, factor in prion disease pathogenesis.
  • Targeting manganese through chelation therapy offers a promising new avenue for treating prion diseases.
  • Further research into the PrP-manganese interaction is warranted to fully understand its implications for disease and therapy.

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