A Drosophila model of Parkinson's disease

被引:1624
作者
Feany, MB
Bender, WW
机构
[1] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
关键词
D O I
10.1038/35006074
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1,2) and alpha-synuclein accumulates in Lewy bodies and Lewy neurites(3-5). 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.
引用
收藏
页码:394 / 398
页数:5
相关论文
共 30 条
  • [1] Baba M, 1998, AM J PATHOL, V152, P879
  • [2] BRAND AH, 1993, DEVELOPMENT, V118, P401
  • [3] DEFECTIVE GLIA IN THE DROSOPHILA BRAIN DEGENERATION MUTANT DROP-DEAD
    BUCHANAN, RL
    BENZER, S
    [J]. NEURON, 1993, 10 (05) : 839 - 850
  • [4] CATECHOLAMINE-CONTAINING NEURONS IN DROSOPHILA-MELANOGASTER - DISTRIBUTION AND DEVELOPMENT
    BUDNIK, V
    WHITE, K
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1988, 268 (03) : 400 - 413
  • [5] BUDNIK V, 1986, J NEUROSCI, V6, P3682
  • [6] Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease
    Conway, KA
    Harper, JD
    Lansbury, PT
    [J]. NATURE MEDICINE, 1998, 4 (11) : 1318 - 1320
  • [7] THE STRUCTURAL BRAIN MUTANT VACUOLAR-MEDULLA OF DROSOPHILA-MELANOGASTER WITH SPECIFIC BEHAVIORAL DEFECTS AND CELL DEGENERATION IN THE ADULT
    COOMBE, PE
    HEISENBERG, M
    [J]. JOURNAL OF NEUROGENETICS, 1986, 3 (03) : 135 - 158
  • [8] DIFFUSE LEWY BODY DISEASE - LIGHT AND ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY OF SENILE PLAQUES
    DICKSON, DW
    CRYSTAL, H
    MATTIACE, LA
    KRESS, Y
    SCHWAGERL, A
    KSIEZAKREDING, H
    DAVIES, P
    YEN, SHC
    [J]. ACTA NEUROPATHOLOGICA, 1989, 78 (06) : 572 - 584
  • [9] Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments
    El-Agnaf, OMA
    Jakes, R
    Curran, MD
    Middleton, D
    Ingenito, R
    Bianchi, E
    Pessi, A
    Neill, D
    Wallace, A
    [J]. FEBS LETTERS, 1998, 440 (1-2) : 71 - 75
  • [10] ELLIS MC, 1993, DEVELOPMENT, V119, P855