Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers |
| |
Authors: | Lee He-Jin Baek Sung Min Ho Dong-Hwan Suk Ji-Eun Cho Eun-Duk Lee Seung-Jae |
| |
Institution: | 1Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.;2Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.;3IBST, Konkuk University, Seoul 143-701, Korea. |
| |
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. |
| |
Keywords: | alpha-synuclein amyloid dopamine Parkinson''s disease protein aggregation secretion |
本文献已被 PubMed 等数据库收录! |
|