A Drosophila Model of Parkinson's Disease

Nature. 2000 Mar 23;404(6776):394-8. doi: 10.1038/35006074.

Abstract

Parkinson's disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the alpha-synuclein gene are linked to familial Parkinson's disease and alpha-synuclein accumulates in Lewy bodies and Lewy neurites. Here we express normal and mutant forms of alpha-synuclein in Drosophila and produce adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing alpha-synuclein and locomotor dysfunction. Our Drosophila model thus recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cloning, Molecular
  • Disease Models, Animal*
  • Dopamine / metabolism
  • Drosophila*
  • Humans
  • Inclusion Bodies / pathology
  • Lewy Bodies / pathology
  • Locomotion
  • Mutation
  • Nerve Degeneration
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Nerve Tissue Proteins / ultrastructure
  • Neurons / metabolism
  • Parkinson Disease* / etiology
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology
  • Retinal Degeneration / etiology
  • Retinal Degeneration / pathology
  • Serotonin / metabolism
  • Synucleins
  • Tyrosine 3-Monooxygenase / metabolism
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • Serotonin
  • Tyrosine 3-Monooxygenase
  • Dopamine