Abstract
Parkinson's disease (PD) is characterized by a selective loss of dopamine-producing neurons in the substantia nigra (SN), which in turn results in dopamine depletion in the striatum, and the presence of neuronal cytoplasmic inclusions known as Lewy bodies (LBs). α-Synuclein is a presynaptic protein that accumulates abnormally in LBs and is seen predominantly in cases of dementia with LBs. Although the central role of α-synuclein in neurodegeneration has been previously demonstrated by the discovery of missense α-synuclein mutations in familial PD, the specific mechanism by which α-synuclein contributes to these diseases remains unclear. In the present study, we examined whether α-synuclein affects the downstream signaling of dopamine D2 receptor (D2R). In CHO cells stably transfected with D2Rs, α-synuclein enhanced dopamine D2-agonist-mediated inhibition of adenylate cyclase, which consequently affected its downstream cAMP-responsive element (CRE)-mediated gene transcription, while C-terminal deletion mutant of α-synuclein did not. Our study suggests that the α-synuclein enhances the dopamine-mediated intracellular signaling pathways by D2R, thus provide a possible mechanism in presynaptic regulation of the synaptic homeostasis in the dopaminergic neurotransmission.
Original language | English |
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Pages (from-to) | 5-9 |
Number of pages | 5 |
Journal | Brain Research |
Volume | 1124 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2006 Dec 8 |
Bibliographical note
Funding Information:This work was supported by a research grant from the basic research grant from KOSEF (Grant No. R01-2004-000-10671-0) and by a grant (Grant No., M103KV010014-06K2201-01410) from the Brain Research Center of the 21st Century Frontier Research Program, funded by the Research Program of the Korean Ministry of Science and Technology. S.J. Kim and Y-S. Na were the recipients of a Brain Korea 21 Program Grant from the Korean Ministry of Education.
Keywords
- Dopamine
- Dopamine D2 receptor
- Signaling
- cAMP
- α-Synuclein
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology