Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers.
10.3858/emm.2011.43.4.026
- Author:
He Jin LEE
1
;
Sung Min BAEK
;
Dong Hwan HO
;
Ji Eun SUK
;
Eun Duk CHO
;
Seung Jae LEE
Author Information
1. Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
alpha-synuclein;
amyloid;
dopamine;
Parkinson's disease;
protein aggregation;
secretion
- MeSH:
Blotting, Western;
Cell Line, Tumor;
Dopamine/*metabolism;
Humans;
Levodopa/pharmacology;
Neurons/*metabolism/pathology/*secretion;
Parkinson Disease/metabolism/pathology;
Substantia Nigra/metabolism/pathology;
alpha-Synuclein/*biosynthesis/*secretion
- From:Experimental & Molecular Medicine
2011;43(4):216-222
- CountryRepublic of Korea
- Language:English
-
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 alpha-synuclein. Previous studies have suggested that DA can interact with alpha-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 alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-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 alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-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.
