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 journalArticle

5 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

Keywords

  • Dopamine
  • Dopamine D2 receptor
  • Signaling
  • cAMP
  • α-Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Jae Kim, S., Yul Kim, S., Na, Y. S., Lee, H. J., Chung, K. C., & Baik, J. H. (2006). α-Synuclein enhances dopamine D2 receptor signaling. Brain Research, 1124(1), 5-9. https://doi.org/10.1016/j.brainres.2006.09.079