Smuggling small molecule modulators of neuroplasticity into appetite-regulating neurons


We know that drugs based on the intestinal hormone GLP-1 effectively target the part of the brain that is key to weight loss, namely the appetite control centre.

“What is spectacular – on a cellular level – about this new drug is the fact that it combines GLP-1 and molecules that block the NMDA receptor. It exploits GLP-1 as a Trojan Horse to smuggle these small molecules exclusively into the neurons that affect appetite control. Without GLP-1, the molecules that target the NMDA receptor would affect the entire brain and thus be non-specific,” says the first author on the study.

Non-specific drugs are often associated with severe side effects, which has previously been seen in drugs for treating different neurobiological conditions.

“A lot of brain disorders are difficult to treat, because the drugs need to cross the so-called blood-brain barrier. Whereas large molecules like peptides and proteins generally have difficulties accessing the brain, many small molecules have unlimited access to the entire brain. We have used the GLP-1 peptide’s specific access to the appetite control centre in the brain to deliver one of these otherwise non-specific substances to this region only,” the author says and adds:

“In this study, we have focused on obesity and weight loss, but in fact this is a completely new approach for delivering drugs to specific parts of the brain. So, I hope our research can pave the way for a whole new class of drugs for treating conditions like neurodegenerative diseases or psychiatric disorders.”

https://www.nature.com/articles/s41586-024-07419-8

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fglp-1-directed-nmda&filter=22

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