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Illuminating the monoamine transporters: Fluorescently labelled ligands to study dopamine, serotonin and norepinephrine transporters

Gisela Andrea Camacho Hernandez , Ph.D.

Study Author Gisela Andrea Camacho Hernandez , Ph.D.

Reviews To Read – January 2023.

Published in Basic & Clinical Pharmacology & Toxicology by Gisela Andrea Camacho-Hernandez , Khorshada Jahan, and Amy Hauck Newman of the NIDA IRP Medicinal Chemistry Section.

The monoamine transporters are proteins that are primarily responsible for the clearance of dopamine, serotonin and norepinephrine, important monoamine neurotransmitters that are involved in key physiological processes. Advancement in our understanding of how these transporters operate in health and disease has been central for the search of medications to treat several neuropsychiatric disorders including, psychostimulant (e.g., cocaine, methamphetamine) use disorders. Fluorescently labeled ligands (FLL) are chemical tools that have been utilized to visualize proteins in living cells. Herein, we describe the design and important characteristics of monoamine transporter-directed FLLs. We highlight the advantages and limitations on how they have been employed as well as future development and potential applications.

Gisela Andrea Camacho-Hernandez; Khorshada Jahan; Amy Hauck Newman

Illuminating the monoamine transporters: Fluorescently labelled ligands to study dopamine, serotonin and norepinephrine transporters Journal Article

In: Basic Clin Pharmacol Toxicol, 2022, ISSN: 1742-7843.

Abstract | Links

@article{pmid36527444,
title = {Illuminating the monoamine transporters: Fluorescently labelled ligands to study dopamine, serotonin and norepinephrine transporters},
author = {Gisela Andrea Camacho-Hernandez and Khorshada Jahan and Amy Hauck Newman},
url = {https://pubmed.ncbi.nlm.nih.gov/36527444/},
doi = {10.1111/bcpt.13827},
issn = {1742-7843},
year = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Basic Clin Pharmacol Toxicol},
abstract = {Fluorescence microscopy has revolutionized the visualization of physiological processes in live-cell systems. With the recent innovations in super resolution microscopy, these events can be examined with high precision and accuracy. The development of fluorescently labelled small molecules has provided a significant advance in understanding the physiological relevance of targeted proteins that can now be visualized at the cellular level. One set of physiologically important target proteins are the monoamine transporters (MATs) that play an instrumental role in maintaining monoamine signalling homeostasis. Understanding the mechanisms underlying their regulation and dysregulation is fundamental to treating several neuropsychiatric conditions such as attention deficit hyperactivity disorder (ADHD), anxiety, depression and substance use disorders. Herein, we describe the rationale behind the small molecule design of fluorescently labelled ligands (FLL) either as MAT substrates or inhibitors as well as their applications to advance our understanding of this class of transporters in health and disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Fluorescence microscopy has revolutionized the visualization of physiological processes in live-cell systems. With the recent innovations in super resolution microscopy, these events can be examined with high precision and accuracy. The development of fluorescently labelled small molecules has provided a significant advance in understanding the physiological relevance of targeted proteins that can now be visualized at the cellular level. One set of physiologically important target proteins are the monoamine transporters (MATs) that play an instrumental role in maintaining monoamine signalling homeostasis. Understanding the mechanisms underlying their regulation and dysregulation is fundamental to treating several neuropsychiatric conditions such as attention deficit hyperactivity disorder (ADHD), anxiety, depression and substance use disorders. Herein, we describe the rationale behind the small molecule design of fluorescently labelled ligands (FLL) either as MAT substrates or inhibitors as well as their applications to advance our understanding of this class of transporters in health and disease.

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  • https://pubmed.ncbi.nlm.nih.gov/36527444/
  • doi:10.1111/bcpt.13827

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