The Structure and Function of the Dopamine Transporter and its Role in CNS Diseases

McHugh, Patrick; Buckley, David

doi:10.1016/bs.vh.2014.12.009

Cited by 61 publications

(51 citation statements)

References 133 publications

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“…The dopamine transporter gene (DAT/SLC6A3) is critical for removal of dopamine in the synapse to halt neurotransmission (German et al, 2015; McHugh and Buckley, 2015). Correspondingly, the disruption of this gene reportedly provokes numerous distinct neuronal pathologies (German et al, 2015; McHugh and Buckley, 2015).…”

Section: Mirna-mediated Regulation Of Dopamine Signaling In Neurologimentioning

confidence: 99%

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Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Carrick

Burks

Cairns

et al. 2016

Front. Mol. Biosci.

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Dopaminergic neurotransmission mediates a majority of the vital central nervous system functions. Disruption of these synaptic events provokes a multitude of neurological pathologies, including Parkinson's, schizophrenia, depression, and addiction. Growing evidence supports a key role for noncoding RNA (ncRNA) regulation in the synapse. This review will discuss the role of both short and long ncRNAs in dopamine signaling, including bioinformatic examination of the pathways they target. Specifically, we focus on the contribution of ncRNAs to dopaminergic dysfunction in neurodegenerative as well as psychiatric disease.

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Section: Mirna-mediated Regulation Of Dopamine Signaling In Neurologimentioning

confidence: 99%

“…Correspondingly, the disruption of this gene reportedly provokes numerous distinct neuronal pathologies (German et al, 2015; McHugh and Buckley, 2015). Two separate studies investigated miRNA binding in polymorphic regions of the DAT gene.…”

Section: Mirna-mediated Regulation Of Dopamine Signaling In Neurologimentioning

confidence: 99%

Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Carrick

Burks

Cairns

et al. 2016

Front. Mol. Biosci.

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“…Dopamine (DA) is one of the principal neurotransmitters in the central nervous system, participating in motion control, emotion, cognition, drug addiction, neuroendocrine regulation, and other vital activities through the activation of DA receptors [1][2][3][4][5][6][7]. Reuptake is a normal mechanism by which neurotransmitters pass through the presynaptic membrane and then are removed from the synaptic cleft [1,2,6,8]. Psychoactive substances block DA reuptake to increase its concentration in the synaptic cleft [2,8].…”

Section: Introductionmentioning

confidence: 99%

“…The 9-and 10-repeat alleles are the most frequently found in the human population [12,14,15]. Changes in the number of copies of this region are closely associated with idiopathic epilepsy, attention-deficit/hyperactivity disorder (ADHD), alcohol and cocaine dependence, susceptibility to Parkinson's disease, and resistance to nicotine dependence [6,11,14,16,17].…”

Section: Introductionmentioning

confidence: 99%

miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells

et al. 2016

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The dopamine transporter (DAT) is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neurotransmission. In the present study, we found that miR-137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine transport. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3'UTR of the DAT and the regulatory effect of miR-491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post-transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.

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“…The availability of dopamine at the synaptic level is regulated by the dopamine active transporter (DAT), a solute carrier protein on presynaptic neurons, which pumps dopamine from neuronal extracellular space into intracellular compartments after release (McHugh & Buckley, 2015). Expression of the DAT protein is shaped by genetic variation of DAT1 gene and thus, it plays a key role in the regulation of dopaminergic neurotransmission, because although exist many dopamine receptors (encoded by genes such as DRD2 and DRD4), exist only one dopamine transporter (Vaughan & Foster, 2013).…”

Section: Dopamine Transportermentioning

confidence: 99%

Dopamine Transporter And Transmission Of Psychopathological Risk. A Review Of Gene-Environment Interplay

Marzilli¹,

Ballarotto²,

Cimino³

et al. 2017

European Proceedings of Social and Behavioural Sciences

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Research underlines that intergenerational transmission of psychopathological risk results from a complex interplay of genetic and environmental risk factors which predispose child to develop emotionalbehavioral problems. Mechanisms of transmission are poorly understood, but few studies have focused on the role played by dopamine transporter (DAT) gene. This review aims to examine mediating mechanism of DAT genotype-environmental interaction (GxE), DAT genotype-environmental correlation (rGE), and methylation status involved in transmission of psychopathological risk. The review of literature was made through researches in university libraries on paper material, and telematics systems research. Studies have evidenced that DAT is implicated in intergenerational transmission of psychopathological risk. Results are mixed regarding its genetic variants, but mechanisms through which this gene can affect both quality of parenting and child development are partially established. Only few studies have examined methylation mechanisms that can be implicated. Findings suggest to involve an improved focus on DAT genotypes, methylation status associated, and their relationship with environment to better understanding child's vulnerability and resilience following exposure to contextual risk factors associated with parental psychopathological symptoms.

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The Structure and Function of the Dopamine Transporter and its Role in CNS Diseases

Cited by 61 publications

References 133 publications

Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells

Dopamine Transporter And Transmission Of Psychopathological Risk. A Review Of Gene-Environment Interplay

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