Imagine if a skyscraper were constructed in such a way where they needed constant maintenance, and if they did not get it would be there natural state to collapse and be destroyed. It seems like a real backwards way to construct a building, or to maintain anything man-made or natural for that matter. So it is surprising to find out that a major chemical signaling pathway, the Wnt and GSK pathway, operates in manner that aligns with this metaphor. The natural state of this critical signaling pathway is that of destruction. The pathway must be activated by a Wnt ligand that triggers cellular events that stop a complex that is involved with destruction. If that seems a bit confusing, I was with you but bear with me. The pathway must be activated, to stop intracellular destruction, which maintains normal cell development.
So why does this matter?
The Wnt signaling pathway is integral in the development of the brain. For example, Schizophrenia is a well-known condition typically associated with disruption of this pathway. Schizophrenia and this pathway, in a nutshell, involves the destruction complex in the cell running wild and not being hindered by Wnt signaling as it should be. This makes sense because there are notable brain changes in schizophrenia involving the anatomy, and key developmental differences. These anatomical changes have some significant consequences for individuals afflicted with such a disease.
Symptoms of Schizophrenia
Most people are familiar with the positive symptoms common of schizophrenia. These would include hearing voices, and grand delusions of government conspiracies for example. These symptoms are only a small part of the wide varieties of symptoms schizophrenia is associated with. For example there are negative symptoms such as flat affect, and low motivation. These symptoms can also be accompanied with cognitive issues which can also have a substantial impact on quality of life.
Cognition and Schizophrenia
Along with positive and negative symptoms, there is a myriad of cognitive deficits typical of schizophrenia some of which are:
- Attention: a common cognitive deficit involved with schizophrenia involves attentional issues. While a neurotypical individual can multitask and focus on several objects, those with schizophrenia tend to hyper-focus on one object at a time.
- Working Memory: Attention and working memory work hand in hand. Working memory is your ability to take in information and briefly maintain and use it in an ongoing task. Generally working memory capacity is 3 to 4 simple items but it is considered less in schizophrenia. If you can only focus on one thing at a time you can only bring that one thing into your memory.
- Executive Functioning: Executive Functioning is a broad and complex topic, but it generally includes things such as planning and goal-oriented behavior. These are all considered impaired in schizophrenia as it is more difficult to bring in new information and adjust to changes.
Conclusion
It is a little wild to think that a simple, and strange signaling pathway going wrong can have such broad consequences for an organism. A signaling pathway gone awry and causing cell death in its resting state is responsible for positive, negative, and cognitive symptoms alike. How such a small molecule, such as the GSK kinase that is responsible for the destruction, can have such broad implication for an overall organism.
