PI3 Kinase and the Prospect of Reversing Memory Loss in Alzheimer's
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Like many proteins of interest to modern life scientists, PI3 kinases (or PI3K) are involved in a whole slew of important metabolic processes. Evolved biology is big on feedback loops and promiscuous reuse of existing components in new mechanisms. So the core controls of metabolism in most species are a rat's nest of connections - proteins and genes with only a single function are a rare breed indeed:

Cancer, diabetes, and aging are related by their use of the PI3K-PTEN-Akt-TOR signaling pathway. This pathway controls how cells grow when nutrients are available and plays a role in how caloric restriction is able to extend lifespan. If parts of the pathway malfunction due to somatic or genetic mutations, cancer or diabetes can result. Thus, the pathway presents an exciting new frontier in medicine as researchers discover how to treat diseases by stopping the propagation of harmful signals and promoting the transmission of beneficial ones.

Research in past years has shown benefits to health and longevity in some species as a result of suppressing forms of PI3K. It's a little early to say why this is the case, but it all looks very similar to many more recently discovered ways of recreating some of the benefits of calorie restriction upon metabolism. That, at least, is the first thought that springs to mind whenever researchers obtain any modest benefit from tinkering with metabolic controls.

Moving further afield, I notice that researchers have made a good step forward in connecting PI3K to the destruction caused by Alzheimer's disease:

Our work suggests that the peptides, or fragments, of β-amyloid associated with Alzheimer's disease directly increase the activity of PI3 kinase, which in turn causes memory loss and increases the accumulation of plaque in the brain.

...

A reduction of this activity via injections of PI3 kinase-blocking drugs or by switching off the gene that encodes PI3 kinase [not] only improved memory in aging fruit flies, but also decreased the buildup of β-amyloid deposits.

These findings on β-amyloid's effect on PI3 kinase activity might explain another mystery about the disease. Among patients, the disease is sometimes known as "brain diabetes" because brain tissue gradually becomes resistant to insulin, further impairing brain function. Insulin is one of the molecules that normally induce PI3-kinase activity, which in turn mediates the cell's response to insulin.

"Our results now suggest that the Alzheimer's brains might become insulin-resistant because PI3 kinase activity is already at the maximum due to its activation by β-amyloid and therefore is no longer able to respond to insulin," explains Zhong. "It might be possible to tackle these various disease symptoms by targeting PI3 kinase."

The tie-in to previous established similarities between Alzheimer's disease and diabetes (including the risk factors - just so you know exactly where that excess body fat and lack of exercise is taking you) is what makes the suggested connections plausible here. If so inclined, you might want to take a look at the original paper. We shall see where it all goes, but I imagine PI3K inhibitors will be in the drug pipeline for this or other reasons not too many years from now.


ResearchBlogging.orgChiang, H., Wang, L., Xie, Z., Yau, A., & Zhong, Y. (2010). PI3 kinase signaling is involved in A -induced memory loss in Drosophila Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0909314107

Comments

I'm sure you are an extremely educated & intelligent person. I only went to college for a few years, but my wife is a Medical Doctor. We both agree we enjoy your articles.Unfortunely we feel your vocabulary is is way to extreme for the aveage reader to understand. It is not the terminolgy but the works you use to explain it. I think most reader would enjoy it more if you focused more on the point instead of trying to impress people with your word dancing.

Posted by: PATRICK MARTIN at March 31, 2010 7:58 AM
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