Is there a cause-and-effect relationship between alpha-synuclein fibrillization and Parkinson's disease?

Nat Cell Biol. 2000 Jul;2(7):E115-9. doi: 10.1038/35017124.


The first gene to be linked to Parkinson's disease encodes the neuronal protein alpha-synuclein. Recent mouse and Drosophila models of Parkinson's disease support a central role for the process of alpha-synuclein fibrillization in pathogenesis. However, some evidence indicates that the fibril itself may not be the pathogenic species. Our own biophysical studies suggest that a structured fibrillization intermediate or an alternatively assembled oligomer may be responsible for neuronal death. This speculation can now be experimentally tested in the animal models. Such experiments will have implications for the development of new therapies for Parkinson's disease and related neurodegenerative diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • Animals
  • Disease Models, Animal*
  • Genetic Predisposition to Disease
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / pathology
  • Ligases*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology*
  • Parkinson Disease / therapy
  • Proteins / genetics
  • Synucleins
  • Thiolester Hydrolases / genetics
  • Ubiquitin Thiolesterase
  • Ubiquitin-Protein Ligases*
  • alpha-Synuclein


  • Nerve Tissue Proteins
  • Proteins
  • SNCA protein, human
  • Snca protein, mouse
  • Synucleins
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase
  • Ligases