A Drosophila model of Parkinson's disease.
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.
Feany
M B
MB
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. mel_feany@hms.harvard.edu
Bender
W W
WW
D000818:Animals; D030801:Animals, Genetically Modified; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004330:Drosophila; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D016631:Lewy Bodies / Q000473:pathology; D008124:Locomotion; D009154:Mutation; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology; D012701:Serotonin / Q000378:metabolism; D051843:Synucleins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine