2017年3月
Potential for targeting dopamine/DARPP-32 signaling in neuropsychiatric and neurodegenerative disorders
EXPERT OPINION ON THERAPEUTIC TARGETS
- ,
- 巻
- 21
- 号
- 3
- 開始ページ
- 259
- 終了ページ
- 272
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1080/14728222.2017.1279149
- 出版者・発行元
- TAYLOR & FRANCIS LTD
Introduction: Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment.Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease. In general, under physiological and pathophysiological conditions, DARPP-32 in D1 receptor expressing (D1R) -medium spiny neurons (MSNs) promotes dopamine/D1 receptor/PKA signaling, whereas DARPP-32 in D2 receptor expressing (D2R)-MSNs counteracts dopamine/D2 receptor signaling. However, the function of DARPP-32 is differentially regulated in acute and chronic phases of drug addiction; DARPP-32 enhances D1 receptor/PKA signaling in the acute phase, whereas DARPP-32 suppresses D1 receptor/PKA signaling in the chronic phase through homeostatic mechanisms. Therefore, DARPP-32 plays a bidirectional role in dopamine neurotransmission, depending on the cell type and experimental conditions, and is involved in dopamine-related behavioral abnormalities.Expert opinion: DARPP-32 differentially regulates dopamine signaling in D1R- and D2R-MSNs, and a shift of balance between D1R- and D2R-MSN function is associated with behavioral abnormalities. An adjustment of this imbalance is achieved by therapeutic approaches targeting DARPP-32-related signaling molecules.
- リンク情報
- ID情報
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- DOI : 10.1080/14728222.2017.1279149
- ISSN : 1472-8222
- eISSN : 1744-7631
- PubMed ID : 28052701
- Web of Science ID : WOS:000395201200005