If there is one thing I’ve learned after reading scientific articles it is that there is always something more I need to learn. Especially after reading the article “Beyond cAMP: The regulation of Akt and GSK3 by Dopamine Receptors”. The article was so thick it was like swimming in a pool of jell-o. But luckily, with some handy tips that my science classes have taught me throughout my years at Concordia, I’ve learned that the only way to eat an elephant is one bite at a time.
Recently, my neurochemistry class read an article about the importance of dopamine and its receptors within a signaling pathway called the Akt/GSK3 pathway. This pathway is involved in all sorts of things such as glucose metabolism, apoptosis, and cell proliferation, transcription and migration.
There are many different kinds of receptors, and the ones most important within the Akt/GSK pathway are the D2 receptors. D2 receptors are a sub family of the dopamine receptors that activate other molecules that eventually inhibit the production of cAMP, an important second messenger molecule involved in many biological processes, and inhibit Akt phosphorylation of GSK3.
Once the D2 receptors are activated, they also inhibit the activation of Akt kinase, which allows the GSK3 kinase to proceed. This is done by the D2 receptors activating a complex, or group of molecules, to form together. This inhibits Akt activation, which means Akt cannot phosphorylate and causes GSK3 to activate.
In certain mood disorders, such as schizophrenia and bipolar disorder, there is an imbalance of dopamine within the brain. Many antipsychotic drugs are used to help this imbalance by working through the Akt/GSK3 pathway. These drugs act as antagonists on the D2 receptors, which causes an increase in Akt activation by not allowing the formation of the inhibitory complex, which in turn decreases GSK3 activity. Thus, too much activation of GSK3 can lead to negative side effects and have been seen to be a possible cause for these disorders.
It’s a lot to understand, especially after tearing the article apart only to simplify it to knowing simple mechanisms when there is so much more going on. But one thing is for sure, the brain is complex and there is always more to learn about it!
Dopamine and the Akt/GSK3 Pathway
