Article ; Online: Turning a Drug Target into a Drug Candidate: A New Paradigm for Neurological Drug Discovery?
BioEssays : news and reviews in molecular, cellular and developmental biology
2020 Volume 42, Issue 9, Page(s) e2000011
Abstract: The conventional paradigm for developing new treatments for disease mainly involves either the discovery of new drug targets, or finding new, improved drugs for old targets. However, an ion channel found only in invertebrates offers the potential of a ... ...
| Abstract | The conventional paradigm for developing new treatments for disease mainly involves either the discovery of new drug targets, or finding new, improved drugs for old targets. However, an ion channel found only in invertebrates offers the potential of a completely new paradigm in which an established drug target can be re-engineered to serve as a new candidate therapeutic agent. The L-glutamate-gated chloride channels (GluCls) of invertebrates are absent from vertebrate genomes, offering the opportunity to introduce this exogenous, inhibitory, L-glutamate receptor into vertebrate neuronal circuits either as a tool with which to study neural networks, or a candidate therapy. Epileptic seizures can involve L-glutamate-induced hyper-excitation and toxicity. Variant GluCls, with their inhibitory responses to L-glutamate, when engineered into human neurons, might counter the excitotoxic effects of excess L-glutamate. In reviewing recent studies on model organisms, it appears that this approach might offer a new paradigm for the development of candidate therapeutics for epilepsy. |
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| MeSH term(s) | Drug Discovery ; Glutamic Acid ; Humans ; Neurons ; Pharmaceutical Preparations |
| Chemical Substances | Pharmaceutical Preparations ; Glutamic Acid (3KX376GY7L) |
| Language | English |
| Publishing date | 2020-08-09 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 50140-2 |
| ISSN | 1521-1878 ; 0265-9247 |
| ISSN (online) | 1521-1878 |
| ISSN | 0265-9247 |
| DOI | 10.1002/bies.202000011 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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