Pathogenesis of Parkinson's disease:: Dopamine, vesicles and α-synuclein

被引:977
作者
Lotharius, J [1 ]
Brundin, P [1 ]
机构
[1] Lund Univ, Dept Physiol Sci, Wallenberg Neurosci Ctr, Sect Neuronal Survival, S-22184 Lund, Sweden
关键词
D O I
10.1038/nrn983
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease is a devastating neurological condition that affects at least four million people. A striking feature of this disorder is the preferential loss of dopamine-producing neurons in the midbrain. Several aetiological triggers have been linked to Parkinson's disease, including genetic mutations and environmental toxins, but the pathway that leads to cell death is unknown. Recent developments have shed light on the pathogenic mechanisms that underlie the degeneration of these cells. We propose that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease, and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
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页码:932 / 942
页数:11
相关论文
共 138 条
  • [1] Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system
    Abeliovich, A
    Schmitz, Y
    Fariñas, I
    Choi-Lundberg, D
    Ho, WH
    Castillo, PE
    Shinsky, N
    Verdugo, JMG
    Armanini, M
    Ryan, A
    Hynes, M
    Phillips, H
    Sulzer, D
    Rosenthal, A
    [J]. NEURON, 2000, 25 (01) : 239 - 252
  • [2] A-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells
    Ahn, BH
    Rhim, H
    Kim, SY
    Sung, YM
    Lee, MY
    Choi, JY
    Wolozin, B
    Chang, JS
    Lee, YH
    Kwon, TK
    Chung, KC
    Yoon, SH
    Hahn, SJ
    Kim, MS
    Jo, YH
    Min, DS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (14) : 12334 - 12342
  • [3] Alam ZI, 1997, J NEUROCHEM, V69, P1326
  • [4] Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra
    Alam, ZI
    Jenner, A
    Daniel, SE
    Lees, AJ
    Cairns, N
    Marsden, CD
    Jenner, P
    Halliwell, B
    [J]. JOURNAL OF NEUROCHEMISTRY, 1997, 69 (03) : 1196 - 1203
  • [5] Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease
    Auluck, PK
    Chan, HYE
    Trojanowski, JQ
    Lee, VMY
    Bonini, NM
    [J]. SCIENCE, 2002, 295 (5556) : 865 - 868
  • [6] Impairment of the ubiquitin-proteasome system by protein aggregation
    Bence, NF
    Sampat, RM
    Kopito, RR
    [J]. SCIENCE, 2001, 292 (5521) : 1552 - 1555
  • [7] IRON MELANIN INTERACTION AND LIPID-PEROXIDATION - IMPLICATIONS FOR PARKINSONS-DISEASE
    BENSHACHAR, D
    RIEDERER, P
    YOUDIM, MBH
    [J]. JOURNAL OF NEUROCHEMISTRY, 1991, 57 (05) : 1609 - 1614
  • [8] Chronic systemic pesticide exposure reproduces features of Parkinson's disease
    Betarbet, R
    Sherer, TB
    MacKenzie, G
    Garcia-Osuna, M
    Panov, AV
    Greenamyre, JT
    [J]. NATURE NEUROSCIENCE, 2000, 3 (12) : 1301 - 1306
  • [9] Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
    Bucciantini, M
    Giannoni, E
    Chiti, F
    Baroni, F
    Formigli, L
    Zurdo, JS
    Taddei, N
    Ramponi, G
    Dobson, CM
    Stefani, M
    [J]. NATURE, 2002, 416 (6880) : 507 - 511
  • [10] Cabin DE, 2002, J NEUROSCI, V22, P8797