Could the insertion of designer receptors at specific brain sites one day potentially aid in permanently restoring proper neuronal network connectivity in certain diseases and disorders?
Sincerely thankful for all your public content, it's greatly enhancing my pharmacology studies.
It's possible, but depends on whether the disease is a result of neuronal loss or not. Obviously adding new receptors won't restore neurons, but it might enhance the activity of the neurons that remain.
Why hasn’t molecular bio post 93 ie SNPs and genotypical receptor selectivity and counter consequence not been mentioned yet? Or is that after the interest-popularity wave?
Because I have to be selective about what I can discuss in a single post and what's pertinent to the topic (and what will make sense to my general readers).
I’m wondering how a DREADD can be so selective even given the mutated structure. Certainly it may have some affinity with additional ligands, whether endogenous or exogenous, right? Is the idea here to simply vastly reduce the number of alternative ligands, and have it be that if there are secondary ligands w/ minor affinity, the effect is so weak that it would not induce intracellular cascades or changes in membrane potential?
Remember, receptors are *already* highly selective: serotonin receptors aren't activated by dopamine or acetylcholine or any other endogenous molecules swimming around in the brain. They're activated by serotonin exclusively, since there are key chemical and spatial arrangements in the binding site required for a molecule to bind and activate the receptor. If you mutate one of these serotonin receptors so it no longer binds serotonin, it's highly unlikely that it will pick up an affinity for some other molecule. So, the vast majority of the mutants created won't bind with significant affinity to *any* endogenous molecules, let alone be activated by them. But, since you can make a lot of mutants, you can select for those rare mutants that happen to bind to (and be activated by) your otherwise inert molecule.
Could the insertion of designer receptors at specific brain sites one day potentially aid in permanently restoring proper neuronal network connectivity in certain diseases and disorders?
Sincerely thankful for all your public content, it's greatly enhancing my pharmacology studies.
It's possible, but depends on whether the disease is a result of neuronal loss or not. Obviously adding new receptors won't restore neurons, but it might enhance the activity of the neurons that remain.
Why hasn’t molecular bio post 93 ie SNPs and genotypical receptor selectivity and counter consequence not been mentioned yet? Or is that after the interest-popularity wave?
Because I have to be selective about what I can discuss in a single post and what's pertinent to the topic (and what will make sense to my general readers).
I’m wondering how a DREADD can be so selective even given the mutated structure. Certainly it may have some affinity with additional ligands, whether endogenous or exogenous, right? Is the idea here to simply vastly reduce the number of alternative ligands, and have it be that if there are secondary ligands w/ minor affinity, the effect is so weak that it would not induce intracellular cascades or changes in membrane potential?
Remember, receptors are *already* highly selective: serotonin receptors aren't activated by dopamine or acetylcholine or any other endogenous molecules swimming around in the brain. They're activated by serotonin exclusively, since there are key chemical and spatial arrangements in the binding site required for a molecule to bind and activate the receptor. If you mutate one of these serotonin receptors so it no longer binds serotonin, it's highly unlikely that it will pick up an affinity for some other molecule. So, the vast majority of the mutants created won't bind with significant affinity to *any* endogenous molecules, let alone be activated by them. But, since you can make a lot of mutants, you can select for those rare mutants that happen to bind to (and be activated by) your otherwise inert molecule.
You go first.