|
KMID : 0620920110430040216
|
|
Experimental & Molecular Medicine
2011 Volume.43 No. 4 p.216 ~ p.222
|
|
|
Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers
|
|
Lee He-Jin
Baek Sung-Min
Ho Dong-Hwan
Suk Ji-Eun
Cho Eun-Duk
Lee Seung-Jae
|
|
|
Abstract
|
|
|
|
Parkinson’s disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of α -synuclein. Previous studies have suggested that DA can interact with α -synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and α -synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human α -synuclein produces non-fibrillar, SDS-resistant oligomers, while β-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted α -synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of α-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of α -synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.
|
|
|
KEYWORD
|
|
|
alpha-synuclein, amyloid, dopamine, Parkinson’s disease, protein aggregation, secretion
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|