It is interesting to think that a single molecule ca
n be a similar variable in a handful of diverse and devastating diseases. It is even more interesting to think that this same molecule is necessary for the control of inflammatory processes in the body. The molecule I am referring to is Nitric Oxide (NO), and it is the main topic of conversation this week in my neurochemistry class. We talked about it in the context of inflammation and a number of other neurodegenerative diseases. I would like to begin by explaining the inflammatory process and why it is important in the body.
The inflammatory response is a process that developed in higher organisms as a mechanism of defense against pathogens and invaders. The response completes a number of tasks:
- It rounds up the necessary cellular components to help manage the cellular damage
- The components localize and eliminate the pathogen or injury-causing stimuli
- Damaged tissue components are removed
- Tissue reconstruction is initiated
In summary, the inflammatory response is necessary for cellular damage to stop and for the body to begin to heal. However, constant or excess inflammation can be extremely harmful to the body, and in particular, the brain. This is why NO is important. It is the molecule that regulates the inflammatory response in the brain. This shows that low levels of it are necessary for proper brain functioning and inflammatory responses.
So, this is why NO needs to be somewhat present in the body. On the other hand, we also discussed the many neurodegenerative diseases that are caused by excess NO. They include:
- Periventricular leukomalacia (PVL)
- Krabbe’s disease
- X-linked adrenoleukodystrophy
- Multiple sclerosis (MS)
In each of these diseases the gene transcribing NO, the iNOS gene, is upregulated. Genes are upregulated by the activation of molecules called transcription factors. The most important one in the upregulation of the iNOS gene is NF-kB. Normally NF-kB is inhibited by being bound to another molecule; however, when it becomes uninhibited it moves into the nucleus to transcribe iNOS. The over transcription of iNOS is the main factor affecting the pathogenesis of these diseases. Furthermore, it is the connecting factor. Each of these diseases is thought to be an imbalance of NO in the brain leading to neurodegeneration.
While all of the diseases produce strikingly different symptoms and signs, it has been found that the underlying neurochemistry has at least one common link, nitric oxide. It has also been found that NO is needed to a certain extent in order to regulate the natural inflammatory response. However, too much of it is harmful and can lead to many different diseases. These conclusions are where research is currently stuck. We are left to determine the correct amount of NO necessary for proper brain function, not too much and not too little. The production of NO by the iNOS gene is a delicate balancing act that can easily fall to one side or the other.
