The solute carrier transporters and the brain: Physiological and pharmacological implications

Hu, Chengliang; Tao, Linmi; Cao, Xizhi; Chen, Ligong

doi:10.1016/j.ajps.2019.09.002

Cited by 119 publications

(104 citation statements)

References 142 publications

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“…Like neurons and glial cells, BBB-forming cells have specific solute carriers. 129 Free thiamine seems to enter the brain via active transport, most likely involving ThTR-2. The transport system is half-saturated at normal plasma concentration of 0.1–0.3 µmol/l.…”

Section: The Journey Of Thiamine Through the Bodymentioning

confidence: 99%

Wernicke’s encephalopathy — from basic science to clinical practice. Part 1: Understanding the role of thiamine

Ott

Werneke

2020

Therapeutic Advances in Psychopharmacology

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Wernicke’s encephalopathy (WE) is an acute neuropsychiatric state. Untreated, WE can lead to coma or death, or progress to Korsakoff syndrome (KS) – a dementia characterized by irreversible loss of anterograde memory. Thiamine (vitamin B1) deficiency lies at the heart of this condition. Yet, our understanding of thiamine regarding prophylaxis and treatment of WE remains limited. This may contribute to the current undertreatment of WE in clinical practice. The overall aim of this review is to identify the best strategies for prophylaxis and treatment of WE in regard to (a) dose of thiamine, (b) mode of administration, (c) timing of switch from one mode of administration to another, (d) duration of administration, and (e) use of magnesium along thiamine as an essential cofactor. Evidence from randomized controlled trials and other intervention studies is virtually absent. Therefore, we have to resort to basic science for proof of principle instead. Here, we present the first part of our clinical review, in which we explore the physiology of thiamine and the pathophysiology of thiamine deficiency. We first explore both of these in their historical context. We then review the pharmacodynamics and pharmacokinetics of thiamine, exploring the roles of the six currently known thiamine compounds, their transporters, and target enzymes. We also explore the significance of magnesium as a cofactor in thiamine-facilitated enzymatic reactions and thiamine transport. In the second (forthcoming) part of this review, we will use the findings of the current review to make evidence-based inferences about strategies for prophylaxis and treatment of WE.

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Section: The Journey Of Thiamine Through the Bodymentioning

confidence: 99%

Wernicke’s encephalopathy — from basic science to clinical practice. Part 1: Understanding the role of thiamine

Ott

Werneke

2020

Therapeutic Advances in Psychopharmacology

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“…The function of SLCs is essential for the homeostasis of the brain, since they participate in energy and glutamate metabolism, neurotransmitter release, blood-brain barrier, etc. (54). Notably, both mice and human studies emphasized the importance of SLC6A15/v7-3 in the development of depression, of which the mechanism is associated with a neuronal circuits alteration that raises susceptibility to depression (55,56).…”

Section: Discussionmentioning

confidence: 99%

Metabonomic Profile and Signaling Pathway Prediction of Depression-Associated Suicidal Behavior

Liu

2020

Front. Psychiatry

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Suicide is the most severe consequence of depression which has become a leading cause of disability and a global disease burden. Recent evidence indicates a central role of small molecules in the pathogenesis of depression and associated suicidal behaviors. However, there lacks a systemic exploration of small molecules in the development of depression-associated suicide, and it remains unclear how they affect an individual's behavior. In order to compare the metabonomic profiles between drug-naïve patients with depression-associated suicidal behaviors and healthy individuals, we conducted a systemic database search for studies of metabolic characteristics in depressionassociated suicidal behavior. Manual data curation and statistical analysis and integration were performed in Excel. We further performed an enrichment analysis of signaling pathway prediction using the Reactome Pathway Analysis tool. We have identified 17 metabolites that expressed differently between drug-naïve patients with depression-associated suicidal behaviors and healthy controls. We have integrated these metabolites into biological signaling pathways and provided a visualized signaling network in depressed suicidal patients. We have revealed that "transport of small molecules", "disease", "metabolism" and "metabolism of proteins" were the most relevant signaling sections, among which "transport of inorganic cations/anions and amino acids/ oligopeptides", "SLC-mediated transmembrane transport", and "metabolism of amino acids and derivatives" should be further studied to elucidate their potential pathogenic mechanism in the development of depression and associated suicidal behavior. In conclusion, our findings of these 17 metabolites and associated signaling pathways could provide an insight into the molecular pathogenesis of depression-associated suicidal behavior and potential targets for new drug inventions.

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“…However, it has become obvious that the endothelial cells that comprise the BBB express numerous transporters to deliver essential nutrients to the brain cells and that such transporters could be exploited for drug delivery. Approximately 300 SLC transporters have been identified in the endothelial cells of BBB and epithelial cells of BCSFB [ 71 ]. Recently, transporter-targeted NDDS have been designed to enhance the permeability of loaded drugs across BBB.…”

Section: Transporter-targeted Ndds For Enhancing Bbb Permeationmentioning

confidence: 99%

“…MCT1 is expressed on the luminal membrane of brain capillary endothelial cells where it plays an essential role in transferring lactate and ketone bodies to the brain [ 71 ]. Venishetty et al explored β-hydroxybutyrate-grafted docetaxel-loaded solid lipid nanoparticles to enhance the drug distribution to the brain [ 69 ].…”

Section: Transporter-targeted Ndds For Enhancing Bbb Permeationmentioning

confidence: 99%

Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery

Kou

Yao

Zhang

et al. 2020

Cancers

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Nano-devices are recognized as increasingly attractive to deliver therapeutics to target cells. The specificity of this approach can be improved by modifying the surface of the delivery vehicles such that they are recognized by the target cells. In the past, cell-surface receptors were exploited for this purpose, but plasma membrane transporters also hold similar potential. Selective transporters are often highly expressed in biological barriers (e.g., intestinal barrier, blood–brain barrier, and blood–retinal barrier) in a site-specific manner, and play a key role in the vectorial transfer of nutrients. Similarly, selective transporters are also overexpressed in the plasma membrane of specific cell types under pathological states to meet the biological needs demanded by such conditions. Nano-drug delivery systems could be strategically modified to make them recognizable by these transporters to enhance the transfer of drugs across the biological barriers or to selectively expose specific cell types to therapeutic drugs. Here, we provide a comprehensive review and detailed evaluation of the recent advances in the field of transporter-targeted nano-drug delivery systems. We specifically focus on areas related to intestinal absorption, transfer across blood–brain barrier, tumor-cell selective targeting, ocular drug delivery, identification of the transporters appropriate for this purpose, and details of the rationale for the approach.

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The solute carrier transporters and the brain: Physiological and pharmacological implications

Cited by 119 publications

References 142 publications

Wernicke’s encephalopathy — from basic science to clinical practice. Part 1: Understanding the role of thiamine

Wernicke’s encephalopathy — from basic science to clinical practice. Part 1: Understanding the role of thiamine

Metabonomic Profile and Signaling Pathway Prediction of Depression-Associated Suicidal Behavior

Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery

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