Role of metal ions in aggregation of intrinsically disordered proteins in neurodegenerative diseases

Metallomics. 2011 Nov;3(11):1163-80. doi: 10.1039/c1mt00106j. Epub 2011 Aug 25.

Abstract

Neurodegenerative diseases constitute a set of pathological conditions originating from the slow, irreversible, and systematic cell loss within the various regions of the brain and/or the spinal cord. Depending on the affected region, the outcomes of the neurodegeneration are very broad and diverse, ranging from the problems with movements to dementia. Some neurodegenerative diseases are associated with protein misfolding and aggregation. Many proteins that misfold in human neurodegenerative diseases are intrinsically disordered; i.e., they lack a stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs) functionally complement ordered proteins, being typically involved in regulation and signaling. There is accumulating evidence that altered metal homeostasis may be related to the progression of neurodegenerative diseases. This review examines the effects of metal ion binding on the aggregation pathways of IDPs found in neurodegenerative diseases.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Ions / chemistry*
  • Metals / chemistry*
  • Molecular Structure
  • Neurodegenerative Diseases / metabolism*
  • Prion Diseases / metabolism
  • Prions / chemistry
  • Prions / metabolism
  • Protein Conformation*
  • Protein Folding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism

Substances

  • Ions
  • Metals
  • Prions
  • Proteins