Akt/GSK3 Cascade: How Important Is It?

While reading the article “Beyond cAMP: the regulation of Akt and GSK3 by dopamine receptor” I thought to myself what on earth does all this technical jargon mean? as this article goes into explicit detail about how the Akt/GSK3 signalling cascade works, what it is intended for, and how understanding this pathway could lead to future pharmacological advances in dopamine-related disorders. The way the article was written made it very difficult for me to digest. By the end of the school week however, I could clearly grasp most of these concepts and most importantly why it was a relevant topic to be discussing.

Akt/GSK3 Pathway Break Down:

1. Initiating the cascade: Dopamine binds to a D2 receptor.

2. β-arrestin, Akt, and PP2A form a complex.

3. PP2A protein dephosphorylates, removing a phosphate group from Akt.

4. This causes Akt to be inhibited meaning Akt cannot phosphorylate GSK3. (When it is phosphorylated it is inhibited)

5. When GSK3 is not phosphorylated it means it will stay activated causing many other cellular responses in the brain.


Who cares about this pathway right?

Wrong! If you are unaware of how important this cascade is in our everyday lives, then you should probably start with the idea that this pathway is necessary for proper human functioning. If this cascade is “out of wack”, it can cause many neurological problems. It has a huge role in the actions of antidepressants, psychostimulants, and antipsychotics. Not only that, but it is involved in the psychopathology of schizophrenia, Parkinson’s disease, and bipolar disorder. Yikes! did you know all of that? I had no idea before reading and discussing this article. Scientists are doing many studies to grasp a better understanding of how this pathway works in hopes that we can find new strategies for the treatment of neurodegenerative disorders as well as finding treatments and cures for many other neurological diseases.

While I do not understand most of the technical jargon associated with the Akt/GSK3 pathway and the dopamine signalling, I do know now that it is extremely important for this pathway to be properly regulated. I also discovered that this is a sort of “hot topic” in the field of neurochemistry. Scientists are making huge discoveries on the role Akt/GSK3 signaling has in dopamine receptor functions and behavior as well as developing new theories as to how this pathway could one day be used to prevent-or at least treat- different neurological diseases. I personally did not know that this pathway was so important. It makes me think about the fact that tiny little molecules and cells in our brain can cause the biggest of problems with our cognition, development, movement, behavior, etc. It literally blows my mind! If one thing within this cascade gets disrupted (intentionally or accidentally) a number of things can happen within the brain, thus affecting the body. For example a person who has decreased dopamine activity in their brain could be at risk for ADHD, Parkinson’s disease, and depression. Is that not crazy how one neurotransmitter can a effect a person in such dramatic ways? This is why  the research in this field is so crucial!