α-Synuclein enhances dopamine D2 receptor signaling

Sung Jae Kim, Sung Yul Kim, Young Soon Na, Hyun Jung Lee, Kwang Chul Chung, Ja Hyun Baik

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)5-9
    Number of pages5
    JournalBrain Research
    Volume1124
    Issue number1
    DOIs
    Publication statusPublished - 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

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