노인성 퇴행성 질환인 Parkinson 씨 병에 관계되는 D1A Dopamine 수용체 유전자의 전사조절에 관한 연구 = Transcription control of the D1A Dopamine receptor gene which is related to Parkinson Disease , the Neurodegenerative Disease

다국어 초록 (Multilingual Abstract)

Dopamine is important for several brain processes including the control of movement, hypothalamic-pituitary axis regulation as well as affect and cognition. Dopamine acts through its seven trans-membrane domain, G-protein coupled receptors coupled to second messenger systems. To date, five dopamine receptor genes have been identified based on their pharmacological profile and sequence homology and classified into two main subfamilies: the D₁, class which includes the D_1A and D_1B (D_5) receptors and the D₂ class which includes D₂, D₃ and D₄ receptors. Among these, the D_1A receptor is one of two dopamine receptors abundantly expressed in the striatum suggesting that it has a critical role in transmitting the nigrostriatal dopaminergic signal resulting in normal motor function. In the prefrontal cortex, the D_1A receptor is more abundantly expressed than the D₂ receptor and has been shown to modulate memory.
Alterations in the expression levels of dopamine receptors could contribute to the manifestations of several neuropsychiatric disorders like Parkinson disease as well as to the complications of their long term therapy. Thus, elucidating the molecular phenomena that control the expression of the D_1A dopamine receptor gene could provide new leads to modulate the dopaminergic system for therapeutic purposes. To study transcription control of the human DIA dopamine receptor gene, we have cloned and characterized its 5` flanking region and analyzed its main activator. We found that in addition to its original TATA-less promoter located upstream of exon 1, the human D_1A dopamine receptor gene is transcribed in neural cells from a second strong promoter located in its intron generating shorter transcripts lacking exon