Opinion: What is the role of protein aggregation in neurodegeneration?

Nat Rev Mol Cell Biol. 2005 Nov;6(11):891-8. doi: 10.1038/nrm1742.


Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Humans
  • Inclusion Bodies / metabolism*
  • Inclusion Bodies / ultrastructure
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology*
  • Proteins / chemistry
  • Proteins / metabolism*


  • Proteins