Circadian Melotonin and Huntington’s Disease

Posted: March 4, 2013 in Uncategorized
Tags: , , , , , ,

This is a continuation from other posts that if you have not seen I encourage you to read them first,https://geneticpotential.wordpress.com/2013/02/27/epigenetics-understanding-gene-expression/,https://geneticpotential.wordpress.com/2013/03/01/summary-of-my-research-so-far/.

Patients with Huntington’s Disease have the survival benefit of increased p53, the tumor suppressing protein.  As I mentioned in previous posts this protein inhibits glucose-6-phosphate dehydrogenase (G6PD).  G6PD has an important role in maintaining glutathione levels and this may be a major part to the pathology of HD.

Glutathione happens to be one of our strongest antioxidants.  Oxidative stress has been implicated as a factor of neurodegeneration along with energy metabolism issues and excitotoxic processess (Browne, 2006).  The reason for the oxidative stress being a culprit may be due to the decrease in glutathione levels.

According to research mutant cells show higher levels of reactive oxygen species (ROS).  This disappeared when glutathione ethyl ester was administered.  Mutant cells show higher levels of reduced and oxidized glutathione when compared to normal cells (Ribeiro, 2012).  Increasing intracellular glutathione may be a way of protecting from neurodegeneration.

Another major player in our glutathione levels is our circadian clock.  Dysregulation in our circadian cycle leads to increased oxidative stress that can cause neurodegeneration.  Sleep disorders are very common in those diagnosed with HD and this may be the reason as well (Beaver, 2012).

This is typically due to low levels of nightime melatonin.  Melatonin may be a very powerful tool in protecting our central nervous system from oxidative damage.  This is due to its ease in crossing the blood-brain barrier.  Melatonin sweeps up oxidants as well as activates other antioxidant enzymes, one of those is glutathione (Reiter, 2006).

In conclusion, oxidative damage is major piece of the pathology seen in HD.  This is due to decreased intracellular glutathione.  Balancing out tissue levels of melatonin may be an important piece to correcting the gluathione levels as melatonin is a regulator of the powerful antioxidant.  Dysfunction in the circadian clock may also explain the high amounts of sleep disturbances seen in HD patients.

 

http://www.ncbi.nlm.nih.gov/m/pubmed/22982598/

http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3639.1999.tb00216.x/abstract

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050454  

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1999.tb08028.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false

Advertisements
Comments
  1. Dan Wren says:

    English, ie. normal person, translation, please.
    You know the science but I, we, do not.
    Thank you..

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s