Wednesday, April 2, 2014

Metals and the Brain I

I have read several papers and books on metal ions in neurodegenerative diseases. So, I decided to start another series of posts as long as I find something to write on the topic.

I just read this article in one of my favorite magazines; The Scientist. I think it is a great review on copper in Alzheimer's disease. I read some of the references long time ago and I think I will read them all as soon as possible. Because, I do not know anything about pharmacology, kinetics of drugs etc., I usually try to understand the structures and read the papers very fast. I do know how to interpret IC50, Ki or other very basic data, graphs or values though. While at it, I should mention that there is a free online medicinal chemistry course on and it is in the 3rd week I guess.

Although we still know little about the true roles and concentrations of the metal ions, new and more powerful techniques (like X-ray fluorescence as the article mentions)  help the scientists to have better information each day. 

Several transition metals are essential for biological processes. One of the most important ones for brain is copper. Actually, the highest concentration of copper in body, is found in brain [1]. So, it is not surprising to see it as a key in neurodegenerative diseases such as Prion diseases, Wilson's disease and Alzheimer's disease. Recently, a group of scientists suggested that zinc is not a biomarker for Alzheimer's Disease. But, as Nigel Hooper says "these data do not rule out a role for altered zinc in the brain being involved in the disease process." Some of the authors of the research article are also working in the same university with the The Scientist article writer. The writer also mentions something similar :
Although overall zinc and iron levels did not vary significantly between AD and healthy brains in Kirsch’s 2011 meta-analysis, this doesn’t rule out complex subcellular changes to the location of these metals.

Even though one can determine the malfunction of the regulation of the metal, the biggest challenge is to fix the problem. One of the methods is using metal complexes (chelates). Here is a library of them by the same author's publication:

In summary, there is a lot of way to find out the cause and the cure for these diseases and I think this is a great article with beautiful infographics and I strongly suggest reading it.

1. Hughes, M.N.; The Inorganic Chemistry of Biological Processes ; Wiley and Sons, 1981;  p 298.

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