Unknown

Dataset Information

0

Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers.


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 ?-synuclein. Previous studies have suggested that DA can interact with ?-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 ?-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human ?-synuclein produces non-fibrillar, SDS-resistant oligomers, while ?-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 ?-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of ?-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of ?-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.

SUBMITTER: Lee HJ 

PROVIDER: S-EPMC3085740 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4071380 | BioStudies
1000-01-01 | S-EPMC2893978 | BioStudies
2020-01-01 | S-EPMC7696693 | BioStudies
2016-01-01 | S-EPMC5011687 | BioStudies
2011-01-01 | S-EPMC3017447 | BioStudies
2017-01-01 | S-EPMC5893155 | BioStudies
1000-01-01 | S-EPMC4099518 | BioStudies
2019-01-01 | S-EPMC6892271 | BioStudies
2019-01-01 | S-EPMC6710741 | BioStudies
2012-01-01 | S-EPMC6493587 | BioStudies