Abnormalities of Dopamine D3 Receptor Signaling in the Diseased Brain

Journal of Central Nervous System Disease

Review

G Aleph Prieto¹ 

[1] G Aleph Prieto, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA. Email: , ;

关键词: Dopamine D receptor;    signaling;    binding;    affinity;    heteromers;    Parkinson’s disease;    essential tremor;    schizophrenia;    addiction;   

DOI  :  10.1177/1179573517726335

 received in 2017-03-27, accepted in 2017-07-19,  发布年份 2017

来源: Sage Journals

【 摘 要 】

Dopamine D3 receptors (D3R) modulate neuronal activity in several brain regions including cortex, striatum, cerebellum, and hippocampus. A growing body of evidence suggests that aberrant D3R signaling contributes to multiple brain diseases, such as Parkinson’s disease, essential tremor, schizophrenia, and addiction. In line with these findings, D3R has emerged as a potential target in the treatment of neurological disorders. However, the mechanisms underlying neuronal D3R signaling are poorly understood, either in healthy or diseased brain. Here, I review the molecular mechanisms involved in D3R signaling via monomeric D3R and heteromeric receptor complexes (e.g., D3R-D1R, D3R-D2R, D3R-A2aR, and D3R-D3nf). I focus on D3R signaling pathways that, according to recent reports, contribute to pathological brain states. In particular, I describe evidence on both quantitative (e.g., increased number or affinity) and qualitative (e.g., switched signaling) changes in D3R that has been associated with brain dysfunction. I conclude with a description of basic mechanisms that modulate D3R signaling such as desensitization, as disruption of these mechanisms may underlie pathological changes in D3R signaling. Because several lines of evidence support the idea that imbalances in D3R signaling alter neural function, a better understanding of downstream D3R pathways is likely to reveal novel therapeutic strategies toward dopamine-related brain disorders.

【 授权许可】

CC BY-NC   
© The Author(s) 2017